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Adipokines, adiposity, and atherosclerosis

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Abstract

Characterized by a surplus of whole-body adiposity, obesity is strongly associated with the prognosis of atherosclerosis, a hallmark of coronary artery disease (CAD) and the major contributor to cardiovascular disease (CVD) mortality. Adipose tissue serves a primary role as a lipid-storage organ, secreting cytokines known as adipokines that affect whole-body metabolism, inflammation, and endocrine functions. Emerging evidence suggests that adipokines can play important roles in atherosclerosis development, progression, as well as regression. Here, we review the versatile functions of various adipokines in atherosclerosis and divide these respective functions into three major groups: protective, deteriorative, and undefined. The protective adipokines represented here are adiponectin, fibroblast growth factor 21 (FGF-21), C1q tumor necrosis factor-related protein 9 (CTRP9), and progranulin, while the deteriorative adipokines listed include leptin, chemerin, resistin, Interleukin- 6 (IL-6), and more, with additional adipokines that have unclear roles denoted as undefined adipokines. Comprehensively categorizing adipokines in the context of atherosclerosis can help elucidate the various pathways involved and potentially pave novel therapeutic approaches to treat CVDs.

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References

  1. World Health Organization (2020) World health statistics 2020: monitoring health for the SDGs, sustainable development goals. World Health Organization. https://apps.who.int/iris/handle/10665/332070. License: CC BY-NC-SA 3.0 IGO

  2. Frostegard J (2013) Immunity, atherosclerosis and cardiovascular disease. BMC Med 11:117

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Tabas I, Lichtman AH (2017) Monocyte-macrophages and T cells in atherosclerosis. Immunity 47(4):621–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Durham AL, Speer MY, Scatena M, Giachelli CM, Shanahan CM (2018) Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness. Cardiovasc Res 114(4):590–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Libby P, Ridker PM, Hansson GK (2009) Leducq transatlantic network on A: inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 54(23):2129–2138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Giorda CB, Avogaro A, Maggini M, Lombardo F, Mannucci E, Turco S, Alegiani SS, Raschetti R, Velussi M, Ferrannini E et al (2008) Recurrence of cardiovascular events in patients with type 2 diabetes: epidemiology and risk factors. Diabetes Care 31(11):2154–2159

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liang W, Ye DD (2019) The potential of adipokines as biomarkers and therapeutic agents for vascular complications in type 2 diabetes mellitus. Cytokine Growth Factor Rev 48:32–39

    Article  CAS  PubMed  Google Scholar 

  8. Ghaben AL, Scherer PE (2019) Adipogenesis and metabolic health. Nat Rev Mol Cell Biol 20(4):242–258

    Article  CAS  PubMed  Google Scholar 

  9. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270(45):26746–26749

    Article  CAS  PubMed  Google Scholar 

  10. Hu E, Liang P, Spiegelman BM (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 271(18):10697–10703

    Article  CAS  PubMed  Google Scholar 

  11. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose most abundant gene transcript 1). Biochem Biophys Res Commun 221(2):286–289

    Article  CAS  PubMed  Google Scholar 

  12. Maahs DM, Ogden LG, Kinney GL, Wadwa P, Snell-Bergeon JK, Dabelea D, Hokanson JE, Ehrlich J, Eckel RH, Rewers M (2005) Low plasma adiponectin levels predict progression of coronary artery calcification. Circulation 111(6):747–753

    Article  CAS  PubMed  Google Scholar 

  13. von Eynatten M, Hamann A, Twardella D, Nawroth PP, Brenner H, Rothenbacher D (2006) Relationship of adiponectin with markers of systemic inflammation, atherogenic dyslipidemia, and heart failure in patients with coronary heart disease. Clin Chem 52(5):853–859

    Article  CAS  Google Scholar 

  14. Patel JV, Abraheem A, Dotsenko O, Creamer J, Gunning M, Hughes EA, Lip GY (2008) Circulating serum adiponectin levels in patients with coronary artery disease: relationship to atherosclerotic burden and cardiac function. J Intern Med 264(6):593–598

    Article  CAS  PubMed  Google Scholar 

  15. Marso SP, Mehta SK, Frutkin A, House JA, McCrary JR, Kulkarni KR (2008) Low adiponectin levels are associated with atherogenic dyslipidemia and lipid-rich plaque in nondiabetic coronary arteries. Diabetes Care 31(5):989–994

    Article  CAS  PubMed  Google Scholar 

  16. Shargorodsky M, Boaz M, Goldberg Y, Matas Z, Gavish D, Fux A, Wolfson N (2009) Adiponectin and vascular properties in obese patients: is it a novel biomarker of early atherosclerosis? Int J Obes (Lond) 33(5):553–558

    Article  CAS  Google Scholar 

  17. Fan LH, He Y, Xu W, Tian HY, Zhou Y, Liang Q, Huang X, Huo JH, Li HB, Bai L et al (2015) Adiponectin may be a biomarker of early atherosclerosis of smokers and decreased by nicotine through KATP channel in adipocytes. Nutrition 31(7–8):955–958

    Article  CAS  PubMed  Google Scholar 

  18. Zhou Y, Wei Y, Wang L, Wang X, Du X, Sun Z, Dong N, Chen X (2011) Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease. Cardiovasc Diabetol 10:2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H et al (2001) Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 103(8):1057–1063

    Article  CAS  PubMed  Google Scholar 

  20. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H et al (2002) Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 106(22):2767–2770

    Article  CAS  PubMed  Google Scholar 

  21. Luo N, Liu J, Chung BH, Yang Q, Klein RL, Garvey WT, Fu Y (2010) Macrophage adiponectin expression improves insulin sensitivity and protects against inflammation and atherosclerosis. Diabetes 59(4):791–799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kobashi C, Urakaze M, Kishida M, Kibayashi E, Kobayashi H, Kihara S, Funahashi T, Takata M, Temaru R, Sato A et al (2005) Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res 97(12):1245–1252

    Article  CAS  PubMed  Google Scholar 

  23. Mahadev K, Wu X, Donnelly S, Ouedraogo R, Eckhart AD, Goldstein BJ (2008) Adiponectin inhibits vascular endothelial growth factor-induced migration of human coronary artery endothelial cells. Cardiovasc Res 78(2):376–384

    Article  CAS  PubMed  Google Scholar 

  24. Nawrocki AR, Hofmann SM, Teupser D, Basford JE, Durand JL, Jelicks LA, Woo CW, Kuriakose G, Factor SM, Tanowitz HB et al (2010) Lack of association between adiponectin levels and atherosclerosis in mice. Arterioscler Thromb Vasc Biol 30(6):1159–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fujishima Y, Maeda N, Matsuda K, Masuda S, Mori T, Fukuda S, Sekimoto R, Yamaoka M, Obata Y, Kita S et al (2017) Adiponectin association with T-cadherin protects against neointima proliferation and atherosclerosis. Faseb j 31(4):1571–1583

    Article  CAS  PubMed  Google Scholar 

  26. Wu X, Qi YF, Chang JR, Lu WW, Zhang JS, Wang SP, Cheng SJ, Zhang M, Fan Q, Lv Y et al (2015) Possible role of fibroblast growth factor 21 on atherosclerosis via amelioration of endoplasmic reticulum stress-mediated apoptosis in apoE(-/-) mice. Heart Vessels 30(5):657–668

    Article  PubMed  Google Scholar 

  27. Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F, Wu J, Kharitonenkov A, Flier JS, Maratos-Flier E et al (2012) FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 26(3):271–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hondares E, Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, Villarroya F (2011) Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J Biol Chem 286(15):12983–12990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tabari FS, Karimian A, Parsian H, Rameshknia V, Mahmoodpour A, Majidinia M, Maniati M, Yousefi B (2019) The roles of FGF21 in atherosclerosis pathogenesis. Rev Endocr Metab Disord 20(1):103–114

    PubMed  Google Scholar 

  30. Jin L, Lin Z, Xu A (2016) Fibroblast growth factor 21 protects against atherosclerosis via fine-tuning the multiorgan crosstalk. Diabetes Metab J 40(1):22–31

    Article  PubMed  PubMed Central  Google Scholar 

  31. Shang W, Yu X, Wang H, Chen T, Fang Y, Yang X, Zhou P, Nie F, Zhou Q, Zhou J (2015) Fibroblast growth factor 21 enhances cholesterol efflux in THP-1 macrophage-derived foam cells. Mol Med Rep 11(1):503–508

    Article  CAS  PubMed  Google Scholar 

  32. Wang N, Li JY, Li S, Guo XC, Wu T, Wang WF, Li DS (2018) Fibroblast growth factor 21 regulates foam cells formation and inflammatory response in Ox-LDL-induced THP-1 macrophages. Biomed Pharmacother 108:1825–1834

    Article  CAS  PubMed  Google Scholar 

  33. Wu L, Qian L, Zhang L, Zhang J, Zhou J, Li Y, Hou X, Fang Q, Li H, Jia W (2020) Fibroblast growth factor 21 is related to atherosclerosis independent of nonalcoholic fatty liver disease and predicts atherosclerotic cardiovascular events. J Am Heart Assoc 9(11):e015226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zeng Z, Zheng Q, Chen J, Tan X, Li Q, Ding L, Zhang R, Lin X (2020) FGF21 mitigates atherosclerosis via inhibition of NLRP3 inflammasome-mediated vascular endothelial cells pyroptosis. Exp Cell Res 393(2):112108

    Article  CAS  PubMed  Google Scholar 

  35. Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, Ge G, Spooner E, Hug C, Gimeno R, Lodish HF (2009) Identification and characterization of CTRP9, a novel secreted glycoprotein, from adipose tissue that reduces serum glucose in mice and forms heterotrimers with adiponectin. FASEB J 23(1):241–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu Q, Zhang H, Lin J, Zhang R, Chen S, Liu W, Sun M, Du W, Hou J, Yu B (2017) C1q/TNF-related protein 9 inhibits the cholesterol-induced vascular smooth muscle cell phenotype switch and cell dysfunction by activating AMP-dependent kinase. J Cell Mol Med 21(11):2823–2836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Uemura Y, Shibata R, Ohashi K, Enomoto T, Kambara T, Yamamoto T, Ogura Y, Yuasa D, Joki Y, Matsuo K et al (2013) Adipose-derived factor CTRP9 attenuates vascular smooth muscle cell proliferation and neointimal formation. Faseb j 27(1):25–33

    Article  CAS  PubMed  Google Scholar 

  38. Wang G, Han B, Zhang R, Liu Q, Wang X, Huang X, Liu D, Qiao W, Yang M, Luo X et al (2021) C1q/TNF-related protein 9 attenuates atherosclerosis by inhibiting hyperglycemia-induced endothelial cell senescence through the ampkalpha/klf4 signaling pathway. Front Pharmacol 12:758792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sun H, Zhu X, Zhou Y, Cai W, Qiu L (2017) C1q/TNF-related protein-9 ameliorates Ox-LDL-induced endothelial dysfunction via PGC-1alpha/AMPK-mediated antioxidant enzyme induction. Int J Mol Sci 18(6):1097

    Article  PubMed Central  CAS  Google Scholar 

  40. Li J, Zhang P, Li T, Liu Y, Zhu Q, Chen T, Liu T, Huang C, Zhang J, Zhang Y et al (2015) CTRP9 enhances carotid plaque stability by reducing pro-inflammatory cytokines in macrophages. Biochem Biophys Res Commun 458(4):890–895

    Article  CAS  PubMed  Google Scholar 

  41. Huang C, Zhang P, Li T, Li J, Liu T, Zuo A, Chen J, Guo Y (2019) Overexpression of CTRP9 attenuates the development of atherosclerosis in apolipoprotein E-deficient mice. Mol Cell Biochem 455(1–2):99–108

    Article  CAS  PubMed  Google Scholar 

  42. Zhang H, Gong X, Ni S, Wang Y, Zhu L, Ji N (2019) C1q/TNF-related protein-9 attenuates atherosclerosis through AMPK-NLRP3 inflammasome singling pathway. Int Immunopharmacol 77:105934

    Article  CAS  PubMed  Google Scholar 

  43. Peterson JM, Wei Z, Seldin MM, Byerly MS, Aja S, Wong GW (2013) CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction. Am J Physiol Regul Integr Comp Physiol 305(5):R522-533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wei Z, Lei X, Petersen PS, Aja S, Wong GW (2014) Targeted deletion of C1q/TNF-related protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice. Am J Physiol Endocrinol Metab 306(7):E779-790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kojima Y, Ono K, Inoue K, Takagi Y, Kikuta K, Nishimura M, Yoshida Y, Nakashima Y, Matsumae H, Furukawa Y et al (2009) Progranulin expression in advanced human atherosclerotic plaque. Atherosclerosis 206(1):102–108

    Article  CAS  PubMed  Google Scholar 

  46. Liu CJ, Bosch X (2012) Progranulin: a growth factor, a novel TNFR ligand and a drug target. Pharmacol Ther 133(1):124–132

    Article  CAS  PubMed  Google Scholar 

  47. Kawase R, Ohama T, Matsuyama A, Matsuwaki T, Okada T, Yamashita T, Yuasa-Kawase M, Nakaoka H, Nakatani K, Inagaki M et al (2013) Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice. Cardiovasc Res 100(1):125–133

    Article  CAS  PubMed  Google Scholar 

  48. Wang BC, Liu H, Talwar A, Jian J (2015) New discovery rarely runs smooth: an update on progranulin/TNFR interactions. Protein Cell 6(11):792–803

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Hwang HJ, Jung TW, Hong HC, Choi HY, Seo JA, Kim SG, Kim NH, Choi KM, Choi DS, Baik SH et al (2013) Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways. PLoS ONE 8(9):e76679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Abella V, Scotece M, Conde J, Lopez V, Pirozzi C, Pino J, Gomez R, Lago F, Gonzalez-Gay MA, Gualillo O (2016) The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1. Sci Rep 6:20356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Nguyen AD, Nguyen TA, Singh RK, Eberle D, Zhang J, Abate JP, Robles A, Koliwad S, Huang EJ, Maxfield FR et al (2018) Progranulin in the hematopoietic compartment protects mice from atherosclerosis. Atherosclerosis 277:145–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372(6505):425–432

    Article  CAS  PubMed  Google Scholar 

  53. Peelman F, Waelput W, Iserentant H, Lavens D, Eyckerman S, Zabeau L, Tavernier J (2004) Leptin: linking adipocyte metabolism with cardiovascular and autoimmune diseases. Prog Lipid Res 43(4):283–301

    Article  CAS  PubMed  Google Scholar 

  54. Reilly MP, Iqbal N, Schutta M, Wolfe ML, Scally M, Localio AR, Rader DJ, Kimmel SE (2004) Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes. J Clin Endocrinol Metab 89(8):3872–3878

    Article  CAS  PubMed  Google Scholar 

  55. McMahon M, Skaggs BJ, Sahakian L, Grossman J, FitzGerald J, Ragavendra N, Charles-Schoeman C, Chernishof M, Gorn A, Witztum JL et al (2011) High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids. Ann Rheum Dis 70(9):1619–1624

    Article  CAS  PubMed  Google Scholar 

  56. Bodary PF, Gu S, Shen Y, Hasty AH, Buckler JM, Eitzman DT (2005) Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 25(8):e119-122

    Article  CAS  PubMed  Google Scholar 

  57. Chiba T, Shinozaki S, Nakazawa T, Kawakami A, Ai M, Kaneko E, Kitagawa M, Kondo K, Chait A, Shimokado K (2008) Leptin deficiency suppresses progression of atherosclerosis in apoE-deficient mice. Atherosclerosis 196(1):68–75

    Article  CAS  PubMed  Google Scholar 

  58. Taleb S, Herbin O, Ait-Oufella H, Verreth W, Gourdy P, Barateau V, Merval R, Esposito B, Clement K, Holvoet P et al (2007) Defective leptin/leptin receptor signaling improves regulatory T cell immune response and protects mice from atherosclerosis. Arterioscler Thromb Vasc Biol 27(12):2691–2698

    Article  CAS  PubMed  Google Scholar 

  59. Singh P, Peterson TE, Sert-Kuniyoshi FH, Jensen MD, Somers VK (2011) Leptin upregulates caveolin-1 expression: implications for development of atherosclerosis. Atherosclerosis 217(2):499–502

    Article  CAS  PubMed  Google Scholar 

  60. Schroeter MR, Leifheit-Nestler M, Hubert A, Schumann B, Glückermann R, Eschholz N, Krüger N, Lutz S, Hasenfuss G, Konstantinides S et al (2013) Leptin promotes neointima formation and smooth muscle cell proliferation via NADPH oxidase activation and signalling in caveolin-rich microdomains. Cardiovasc Res 99(3):555–565

    Article  CAS  PubMed  Google Scholar 

  61. Ganguly R, Khanal S, Mathias A, Gupta S, Lallo J, Sahu S, Ohanyan V, Patel A, Storm K, Datta S et al (2021) TSP-1 (thrombospondin-1) deficiency protects ApoE(-/-) mice against leptin-induced atherosclerosis. Arterioscler Thromb Vasc Biol 41(2):e112–e127

    Article  CAS  PubMed  Google Scholar 

  62. Martin SS, Blaha MJ, Muse ED, Qasim AN, Reilly MP, Blumenthal RS, Nasir K, Criqui MH, McClelland RL, Hughes-Austin JM et al (2015) Leptin and incident cardiovascular disease: the multi-ethnic study of atherosclerosis (MESA). Atherosclerosis 239(1):67–72

    Article  CAS  PubMed  Google Scholar 

  63. Hasty AH, Shimano H, Osuga J, Namatame I, Takahashi A, Yahagi N, Perrey S, Iizuka Y, Tamura Y, Amemiya-Kudo M et al (2001) Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor. J Biol Chem 276(40):37402–37408

    Article  CAS  PubMed  Google Scholar 

  64. Jun JY, Ma Z, Pyla R, Segar L (2012) Leptin treatment inhibits the progression of atherosclerosis by attenuating hypercholesterolemia in type 1 diabetic Ins2(+/Akita):apoE(-/-) mice. Atherosclerosis 225(2):341–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Luo W, Bodary PF, Shen Y, Wickenheiser KJ, Ohman MK, Guo C, Bahrou KL, Myers MG Jr, Eitzman DT (2011) Leptin receptor-induced STAT3-independent signaling pathways are protective against atherosclerosis in a murine model of obesity and hyperlipidemia. Atherosclerosis 214(1):81–85

    Article  CAS  PubMed  Google Scholar 

  66. Vernochet C, Peres SB, Davis KE, McDonald ME, Qiang L, Wang H, Scherer PE, Farmer SR (2009) C/EBPalpha and the corepressors CtBP1 and CtBP2 regulate repression of select visceral white adipose genes during induction of the brown phenotype in white adipocytes by peroxisome proliferator-activated receptor gamma agonists. Mol Cell Biol 29(17):4714–4728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lehrke M, Becker A, Greif M, Stark R, Laubender RP, von Ziegler F, Lebherz C, Tittus J, Reiser M, Becker C et al (2009) Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis. Eur J Endocrinol 161(2):339–344

    Article  CAS  PubMed  Google Scholar 

  68. Gu P, Cheng M, Hui X, Lu B, Jiang W, Shi Z (2015) Elevating circulation chemerin level is associated with endothelial dysfunction and early atherosclerotic changes in essential hypertensive patients. J Hypertens 33(8):1624–1632

    Article  CAS  PubMed  Google Scholar 

  69. Gao X, Mi S, Zhang F, Gong F, Lai Y, Gao F, Zhang X, Wang L, Tao H (2011) Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis. Cardiovasc Diabetol 10:87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Liu H, Xiong W, Luo Y, Chen H, He Y, Cao Y, Dong S (2019) Adipokine chemerin stimulates progression of atherosclerosis in ApoE(-/-) mice. Biomed Res Int 2019:7157865

    PubMed  PubMed Central  Google Scholar 

  71. Zhou L, Li JY, He PP, Yu XH, Tang CK (2021) Resistin: potential biomarker and therapeutic target in atherosclerosis. Clin Chim Acta 512:84–91

    Article  CAS  PubMed  Google Scholar 

  72. Efstathiou SP, Tsiakou AG, Tsioulos DI, Panagiotou TN, Pefanis AV, Achimastos AD, Mountokalakis TD (2007) Prognostic significance of plasma resistin levels in patients with atherothrombotic ischemic stroke. Clin Chim Acta 378(1–2):78–85

    Article  CAS  PubMed  Google Scholar 

  73. Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ (2005) Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111(7):932–939

    Article  CAS  PubMed  Google Scholar 

  74. Sabry MM, Dawood AF, Rashed LA, Sayed SM, Hassan S, Younes SF (2020) Relation between resistin, PPAR-gamma, obesity and atherosclerosis in male albino rats. Arch Physiol Biochem 126(5):389–398

    Article  CAS  PubMed  Google Scholar 

  75. Cho Y, Lee SE, Lee HC, Hur J, Lee S, Youn SW, Lee J, Lee HJ, Lee TK, Park J et al (2011) Adipokine resistin is a key player to modulate monocytes, endothelial cells, and smooth muscle cells, leading to progression of atherosclerosis in rabbit carotid artery. J Am Coll Cardiol 57(1):99–109

    Article  CAS  PubMed  Google Scholar 

  76. Asterholm IW, Rutkowski JM, Fujikawa T, Cho YR, Fukuda M, Tao C, Wang ZV, Gupta RK, Elmquist JK, Scherer PE (2014) Elevated resistin levels induce central leptin resistance and increased atherosclerotic progression in mice. Diabetologia 57(6):1209–1218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Burnett MS, Lee CW, Kinnaird TD, Stabile E, Durrani S, Dullum MK, Devaney JM, Fishman C, Stamou S, Canos D et al (2005) The potential role of resistin in atherogenesis. Atherosclerosis 182(2):241–248

    Article  CAS  PubMed  Google Scholar 

  78. Hirai H, Satoh H, Kudoh A, Watanabe T (2013) Interaction between resistin and adiponectin in the proliferation of rat vascular smooth muscle cells. Mol Cell Endocrinol 366(1):108–116

    Article  CAS  PubMed  Google Scholar 

  79. Liberale L, Bertolotto M, Carbone F, Contini P, Wust P, Spinella G, Pane B, Palombo D, Bonaventura A, Pende A et al (2018) Resistin exerts a beneficial role in atherosclerotic plaque inflammation by inhibiting neutrophil migration. Int J Cardiol 272:13–19

    Article  PubMed  Google Scholar 

  80. Cook JS, Lucas JJ, Sibley E, Bolanowski MA, Christy RJ, Kelly TJ, Lane MD (1988) Expression of the differentiation-induced gene for fatty acid-binding protein is activated by glucocorticoid and cAMP. Proc Natl Acad Sci U S A 85(9):2949–2953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Amri EZ, Bertrand B, Ailhaud G, Grimaldi P (1991) Regulation of adipose cell differentiation. I. Fatty acids are inducers of the aP2 gene expression. J Lipid Res 32(9):1449–1456

    Article  CAS  PubMed  Google Scholar 

  82. Distel RJ, Robinson GS, Spiegelman BM (1992) Fatty acid regulation of gene expression. Transcriptional and post-transcriptional mechanisms. J Biol Chem 267(9):5937–5941

    Article  CAS  PubMed  Google Scholar 

  83. Kletzien RF, Foellmi LA, Harris PK, Wyse BM, Clarke SD (1992) Adipocyte fatty acid-binding protein: regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent. Mol Pharmacol 42(4):558–562

    CAS  PubMed  Google Scholar 

  84. Hotamisligil GS, Johnson RS, Distel RJ, Ellis R, Papaioannou VE, Spiegelman BM (1996) Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 274(5291):1377–1379

    Article  CAS  PubMed  Google Scholar 

  85. Uysal KT, Scheja L, Wiesbrock SM, Bonner-Weir S, Hotamisligil GS (2000) Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology 141(9):3388–3396

    Article  CAS  PubMed  Google Scholar 

  86. Furuhashi M, Fucho R, Gorgun CZ, Tuncman G, Cao H, Hotamisligil GS (2008) Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J Clin Invest 118(7):2640–2650

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Xu A, Wang Y, Xu JY, Stejskal D, Tam S, Zhang J, Wat NM, Wong WK, Lam KS (2006) Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem 52(3):405–413

    Article  CAS  PubMed  Google Scholar 

  88. Yeung DC, Xu A, Tso AW, Chow WS, Wat NM, Fong CH, Tam S, Sham PC, Lam KS (2009) Circulating levels of adipocyte and epidermal fatty acid-binding proteins in relation to nephropathy staging and macrovascular complications in type 2 diabetic patients. Diabetes Care 32(1):132–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Yeung DC, Wang Y, Xu A, Cheung SC, Wat NM, Fong DY, Fong CH, Chau MT, Sham PC, Lam KS (2008) Epidermal fatty-acid-binding protein: a new circulating biomarker associated with cardio-metabolic risk factors and carotid atherosclerosis. Eur Heart J 29(17):2156–2163

    Article  CAS  PubMed  Google Scholar 

  90. Hao Y, Ma X, Luo Y, Shen Y, Dou J, Pan X, Bao Y, Jia W (2014) Serum adipocyte fatty acid binding protein levels are positively associated with subclinical atherosclerosis in Chinese pre- and postmenopausal women with normal glucose tolerance. J Clin Endocrinol Metab 99(11):4321–4327

    Article  CAS  PubMed  Google Scholar 

  91. von Eynatten M, Breitling LP, Roos M, Baumann M, Rothenbacher D, Brenner H (2012) Circulating adipocyte fatty acid-binding protein levels and cardiovascular morbidity and mortality in patients with coronary heart disease: a 10-year prospective study. Arterioscler Thromb Vasc Biol 32(9):2327–2335

    Article  CAS  Google Scholar 

  92. Hui X, Li H, Zhou Z, Lam KS, Xiao Y, Wu D, Ding K, Wang Y, Vanhoutte PM, Xu A (2010) Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH2-terminal kinases and activator protein-1. J Biol Chem 285(14):10273–10280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Layne MD, Patel A, Chen YH, Rebel VI, Carvajal IM, Pellacani A, Ith B, Zhao D, Schreiber BM, Yet SF et al (2001) Role of macrophage-expressed adipocyte fatty acid binding protein in the development of accelerated atherosclerosis in hypercholesterolemic mice. FASEB J 15(14):2733–2735

    Article  CAS  PubMed  Google Scholar 

  94. Dinarello CA (2011) A clinical perspective of IL-1beta as the gatekeeper of inflammation. Eur J Immunol 41(5):1203–1217

    Article  CAS  PubMed  Google Scholar 

  95. Beaulieu LM, Lin E, Mick E, Koupenova M, Weinberg EO, Kramer CD, Genco CA, Tanriverdi K, Larson MG, Benjamin EJ et al (2014) Interleukin 1 receptor 1 and interleukin 1beta regulate megakaryocyte maturation, platelet activation, and transcript profile during inflammation in mice and humans. Arterioscler Thromb Vasc Biol 34(3):552–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Latz E, Xiao TS, Stutz A (2013) Activation and regulation of the inflammasomes. Nat Rev Immunol 13(6):397–411

    Article  CAS  PubMed  Google Scholar 

  97. Paramel Varghese G, Folkersen L, Strawbridge RJ, Halvorsen B, Yndestad A, Ranheim T, Krohg-Sorensen K, Skjelland M, Espevik T, Aukrust P et al (2016) NLRP3 inflammasome expression and activation in human atherosclerosis. J Am Heart Assoc. https://doi.org/10.1161/JAHA.115.003031

    Article  PubMed  PubMed Central  Google Scholar 

  98. Qiao L, Ma J, Zhang Z, Sui W, Zhai C, Xu D, Wang Z, Lu H, Zhang M, Zhang C et al (2021) Deficient chaperone-mediated autophagy promotes inflammation and atherosclerosis. Circ Res 129(12):1141–1157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Kirii H, Niwa T, Yamada Y, Wada H, Saito K, Iwakura Y, Asano M, Moriwaki H, Seishima M (2003) Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 23(4):656–660

    Article  CAS  PubMed  Google Scholar 

  100. Kamari Y, Shaish A, Shemesh S, Vax E, Grosskopf I, Dotan S, White M, Voronov E, Dinarello CA, Apte RN et al (2011) Reduced atherosclerosis and inflammatory cytokines in apolipoprotein-E-deficient mice lacking bone marrow-derived interleukin-1alpha. Biochem Biophys Res Commun 405(2):197–203

    Article  CAS  PubMed  Google Scholar 

  101. Vromman A, Ruvkun V, Shvartz E, Wojtkiewicz G, Santos Masson G, Tesmenitsky Y, Folco E, Gram H, Nahrendorf M, Swirski FK et al (2019) Stage-dependent differential effects of interleukin-1 isoforms on experimental atherosclerosis. Eur Heart J 40(30):2482–2491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Gomez D, Baylis RA, Durgin BG, Newman AAC, Alencar GF, Mahan S, St Hilaire C, Muller W, Waisman A, Francis SE et al (2018) Interleukin-1beta has atheroprotective effects in advanced atherosclerotic lesions of mice. Nat Med 24(9):1418–1429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Ceneri N, Zhao L, Young BD, Healy A, Coskun S, Vasavada H, Yarovinsky TO, Ike K, Pardi R, Qin L et al (2017) Rac2 modulates atherosclerotic calcification by regulating macrophage interleukin-1beta production. Arterioscler Thromb Vasc Biol 37(2):328–340

    Article  CAS  PubMed  Google Scholar 

  104. Isoda K, Shiigai M, Ishigami N, Matsuki T, Horai R, Nishikawa K, Kusuhara M, Nishida Y, Iwakura Y, Ohsuzu F (2003) Deficiency of interleukin-1 receptor antagonist promotes neointimal formation after injury. Circulation 108(5):516–518

    Article  CAS  PubMed  Google Scholar 

  105. Chamberlain J, Evans D, King A, Dewberry R, Dower S, Crossman D, Francis S (2006) Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice. Am J Pathol 168(4):1396–1403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Viana-Huete V, Fuster JJ (2019) Potential therapeutic value of interleukin 1b-targeted strategies in atherosclerotic cardiovascular disease. Rev Esp Cardiol (Engl Ed) 72(9):760–766

    Article  Google Scholar 

  107. Bhat OM, Kumar PU, Giridharan NV, Kaul D, Kumar MJ, Dhawan V (2015) Interleukin-18-induced atherosclerosis involves CD36 and NF-kappaB crosstalk in Apo E-/- mice. J Cardiol 66(1):28–35

    Article  PubMed  Google Scholar 

  108. Mallat Z, Corbaz A, Scoazec A, Besnard S, Leseche G, Chvatchko Y, Tedgui A (2001) Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation 104(14):1598–1603

    Article  CAS  PubMed  Google Scholar 

  109. Formanowicz D, Rybarczyk A, Radom M, Tanas K, Formanowicz P (2020) A stochastic petri net-based model of the involvement of interleukin 18 in atherosclerosis. Int J Mol Sci 21(22):8574

    Article  CAS  PubMed Central  Google Scholar 

  110. Hulthe J, McPheat W, Samnegard A, Tornvall P, Hamsten A, Eriksson P (2006) Plasma interleukin (IL)-18 concentrations is elevated in patients with previous myocardial infarction and related to severity of coronary atherosclerosis independently of C-reactive protein and IL-6. Atherosclerosis 188(2):450–454

    Article  CAS  PubMed  Google Scholar 

  111. Tiret L, Godefroy T, Lubos E, Nicaud V, Tregouet DA, Barbaux S, Schnabel R, Bickel C, Espinola-Klein C, Poirier O et al (2005) Genetic analysis of the interleukin-18 system highlights the role of the interleukin-18 gene in cardiovascular disease. Circulation 112(5):643–650

    Article  CAS  PubMed  Google Scholar 

  112. Mallat Z, Corbaz A, Scoazec A, Graber P, Alouani S, Esposito B, Humbert Y, Chvatchko Y, Tedgui A (2001) Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability. Circ Res 89(7):E41-45

    Article  CAS  PubMed  Google Scholar 

  113. Whitman SC, Ravisankar P, Daugherty A (2002) Interleukin-18 enhances atherosclerosis in apolipoprotein E(-/-) mice through release of interferon-gamma. Circ Res 90(2):E34-38

    Article  CAS  PubMed  Google Scholar 

  114. Tenger C, Sundborger A, Jawien J, Zhou X (2005) IL-18 accelerates atherosclerosis accompanied by elevation of IFN-gamma and CXCL16 expression independently of T cells. Arterioscler Thromb Vasc Biol 25(4):791–796

    Article  CAS  PubMed  Google Scholar 

  115. Wang J, Sun C, Gerdes N, Liu C, Liao M, Liu J, Shi MA, He A, Zhou Y, Sukhova GK et al (2015) Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter. Nat Med 21(7):820–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Troseid M, Seljeflot I, Weiss TW, Klemsdal TO, Hjerkinn EM, Arnesen H (2010) Arterial stiffness is independently associated with interleukin-18 and components of the metabolic syndrome. Atherosclerosis 209(2):337–339

    Article  CAS  PubMed  Google Scholar 

  117. Zirlik A, Abdullah SM, Gerdes N, MacFarlane L, Schonbeck U, Khera A, McGuire DK, Vega GL, Grundy S, Libby P et al (2007) Interleukin-18, the metabolic syndrome, and subclinical atherosclerosis: results from the Dallas heart study. Arterioscler Thromb Vasc Biol 27(9):2043–2049

    Article  CAS  PubMed  Google Scholar 

  118. Suo F, Jiang F, Fang X, Ma A, Ma L (2019) Contrast of diagnostic value between IL-17 combined with IL-18 and CT angiography in carotid atherosclerosis. Exp Ther Med 17(2):1400–1404

    CAS  PubMed  Google Scholar 

  119. Madan M, Bishayi B, Hoge M, Amar S (2008) Atheroprotective role of interleukin-6 in diet- and/or pathogen-associated atherosclerosis using an ApoE heterozygote murine model. Atherosclerosis 197(2):504–514

    Article  CAS  PubMed  Google Scholar 

  120. Schieffer B, Selle T, Hilfiker A, Hilfiker-Kleiner D, Grote K, Tietge UJ, Trautwein C, Luchtefeld M, Schmittkamp C, Heeneman S et al (2004) Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis. Circulation 110(22):3493–3500

    Article  CAS  PubMed  Google Scholar 

  121. Lee WY, Allison MA, Kim DJ, Song CH, Barrett-Connor E (2007) Association of interleukin-6 and C-reactive protein with subclinical carotid atherosclerosis (the Rancho Bernardo study). Am J Cardiol 99(1):99–102

    Article  CAS  PubMed  Google Scholar 

  122. Wassmann S, Stumpf M, Strehlow K, Schmid A, Schieffer B, Bohm M, Nickenig G (2004) Interleukin-6 induces oxidative stress and endothelial dysfunction by overexpression of the angiotensin II type 1 receptor. Circ Res 94(4):534–541

    Article  CAS  PubMed  Google Scholar 

  123. Huber SA, Sakkinen P, Conze D, Hardin N, Tracy R (1999) Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscler Thromb Vasc Biol 19(10):2364–2367

    Article  CAS  PubMed  Google Scholar 

  124. Tyrrell DJ, Blin MG, Song J, Wood SC, Zhang M, Beard DA, Goldstein DR (2020) Age-associated mitochondrial dysfunction accelerates atherogenesis. Circ Res 126(3):298–314

    Article  CAS  PubMed  Google Scholar 

  125. Tyrrell DJ, Goldstein DR (2021) Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6. Nat Rev Cardiol 18(1):58–68

    Article  CAS  PubMed  Google Scholar 

  126. Schuett H, Oestreich R, Waetzig GH, Annema W, Luchtefeld M, Hillmer A, Bavendiek U, von Felden J, Divchev D, Kempf T et al (2012) Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice. Arterioscler Thromb Vasc Biol 32(2):281–290

    Article  CAS  PubMed  Google Scholar 

  127. Biros E, Reznik JE, Moran CS (2021) Role of inflammatory cytokines in genesis and treatment of atherosclerosis. Trends Cardiovasc Med. https://doi.org/10.1016/j.tcm.2021.02.001

    Article  PubMed  Google Scholar 

  128. Pedersen ER, Midttun O, Ueland PM, Schartum-Hansen H, Seifert R, Igland J, Nordrehaug JE, Ebbing M, Svingen G, Bleie O et al (2011) Systemic markers of interferon-gamma-mediated immune activation and long-term prognosis in patients with stable coronary artery disease. Arterioscler Thromb Vasc Biol 31(3):698–704

    Article  CAS  PubMed  Google Scholar 

  129. Harvey EJ, Ramji DP (2005) Interferon-gamma and atherosclerosis: pro- or anti-atherogenic? Cardiovasc Res 67(1):11–20

    Article  CAS  PubMed  Google Scholar 

  130. McLaren JE, Ramji DP (2009) Interferon gamma: a master regulator of atherosclerosis. Cytokine Growth Factor Rev 20(2):125–135

    Article  CAS  PubMed  Google Scholar 

  131. Voloshyna I, Littlefield MJ, Reiss AB (2014) Atherosclerosis and interferon-gamma: new insights and therapeutic targets. Trends Cardiovasc Med 24(1):45–51

    Article  CAS  PubMed  Google Scholar 

  132. Yu XH, Zhang J, Zheng XL, Yang YH, Tang CK (2015) Interferon-gamma in foam cell formation and progression of atherosclerosis. Clin Chim Acta 441:33–43

    Article  CAS  PubMed  Google Scholar 

  133. Elyasi A, Voloshyna I, Ahmed S, Kasselman LJ, Behbodikhah J, De Leon J, Reiss AB (2020) The role of interferon-gamma in cardiovascular disease: an update. Inflamm Res 69(10):975–988

    Article  CAS  PubMed  Google Scholar 

  134. Kushiyama A, Sakoda H, Oue N, Okubo M, Nakatsu Y, Ono H, Fukushima T, Kamata H, Nishimura F, Kikuchi T et al (2013) Resistin-like molecule beta is abundantly expressed in foam cells and is involved in atherosclerosis development. Arterioscler Thromb Vasc Biol 33(8):1986–1993

    Article  CAS  PubMed  Google Scholar 

  135. Lee LY, Oldham WM, He H, Wang R, Mulhern R, Handy DE, Loscalzo J (2021) Interferon-gamma impairs human coronary artery endothelial glucose metabolism by tryptophan catabolism and activates fatty acid oxidation. Circulation 144(20):1612–1628

    Article  PubMed  Google Scholar 

  136. Saez JC, Contreras-Duarte S, Labra VC, Santibanez CA, Mellado LA, Inostroza CA, Alvear TF, Retamal MA, Velarde V, Orellana JA (2020) Interferon-gamma and high glucose-induced opening of Cx43 hemichannels causes endothelial cell dysfunction and damage. Biochim Biophys Acta Mol Cell Res 1867(8):118720

    Article  CAS  PubMed  Google Scholar 

  137. Buono C, Come CE, Stavrakis G, Maguire GF, Connelly PW, Lichtman AH (2003) Influence of interferon-gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse. Arterioscler Thromb Vasc Biol 23(3):454–460

    Article  CAS  PubMed  Google Scholar 

  138. Whitman SC, Ravisankar P, Daugherty A (2002) IFN-gamma deficiency exerts gender-specific effects on atherogenesis in apolipoprotein E-/- mice. J Interferon Cytokine Res 22(6):661–670

    Article  CAS  PubMed  Google Scholar 

  139. Niwa T, Wada H, Ohashi H, Iwamoto N, Ohta H, Kirii H, Fujii H, Saito K, Seishima M (2004) Interferon-gamma produced by bone marrow-derived cells attenuates atherosclerotic lesion formation in LDLR-deficient mice. J Atheroscler Thromb 11(2):79–87

    Article  CAS  PubMed  Google Scholar 

  140. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259(5091):87–91

    Article  CAS  PubMed  Google Scholar 

  141. Tintut Y, Patel J, Parhami F, Demer LL (2000) Tumor necrosis factor-alpha promotes in vitro calcification of vascular cells via the cAMP pathway. Circulation 102(21):2636–2642

    Article  CAS  PubMed  Google Scholar 

  142. Branen L, Hovgaard L, Nitulescu M, Bengtsson E, Nilsson J, Jovinge S (2004) Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 24(11):2137–2142

    Article  CAS  PubMed  Google Scholar 

  143. Ohta H, Wada H, Niwa T, Kirii H, Iwamoto N, Fujii H, Saito K, Sekikawa K, Seishima M (2005) Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis 180(1):11–17

    Article  CAS  PubMed  Google Scholar 

  144. Suganami T, Nishida J, Ogawa Y (2005) A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 25(10):2062–2068

    Article  CAS  PubMed  Google Scholar 

  145. Zhang L, Peppel K, Sivashanmugam P, Orman ES, Brian L, Exum ST, Freedman NJ (2007) Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis. Arterioscler Thromb Vasc Biol 27(5):1087–1094

    Article  PubMed  PubMed Central  Google Scholar 

  146. Xiao N, Yin M, Zhang L, Qu X, Du H, Sun X, Mao L, Ren G, Zhang C, Geng Y et al (2009) Tumor necrosis factor-alpha deficiency retards early fatty-streak lesion by influencing the expression of inflammatory factors in apoE-null mice. Mol Genet Metab 96(4):239–244

    Article  CAS  PubMed  Google Scholar 

  147. Zhang Y, Yang X, Bian F, Wu P, Xing S, Xu G, Li W, Chi J, Ouyang C, Zheng T et al (2014) TNF-α promotes early atherosclerosis by increasing transcytosis of LDL across endothelial cells: crosstalk between NF-κB and PPAR-γ. J Mol Cell Cardiol 72:85–94

    Article  CAS  PubMed  Google Scholar 

  148. Gao W, Liu H, Yuan J, Wu C, Huang D, Ma Y, Zhu J, Ma L, Guo J, Shi H et al (2016) Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF-alpha mediated NF-kappaB pathway. J Cell Mol Med 20(12):2318–2327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Tay C, Liu YH, Hosseini H, Kanellakis P, Cao A, Peter K, Tipping P, Bobik A, Toh BH, Kyaw T (2016) B-cell-specific depletion of tumour necrosis factor alpha inhibits atherosclerosis development and plaque vulnerability to rupture by reducing cell death and inflammation. Cardiovasc Res 111(4):385–397

    Article  CAS  PubMed  Google Scholar 

  150. Blessing E, Bea F, Kuo CC, Campbell LA, Chesebro B, Rosenfeld ME (2004) Lesion progression and plaque composition are not altered in older apoE-/- mice lacking tumor necrosis factor-alpha receptor p55. Atherosclerosis 176(2):227–232

    Article  CAS  PubMed  Google Scholar 

  151. Eitzman DT, Westrick RJ, Xu Z, Tyson J, Ginsburg D (2000) Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery. Blood 96(13):4212–4215

    Article  CAS  PubMed  Google Scholar 

  152. DeYoung MB, Tom C, Dichek DA (2001) Plasminogen activator inhibitor type 1 increases neointima formation in balloon-injured rat carotid arteries. Circulation 104(16):1972–1971

    Article  CAS  PubMed  Google Scholar 

  153. Zhu Y, Farrehi PM, Fay WP (2001) Plasminogen activator inhibitor type 1 enhances neointima formation after oxidative vascular injury in atherosclerosis-prone mice. Circulation 103(25):3105–3110

    Article  CAS  PubMed  Google Scholar 

  154. Schafer K, Muller K, Hecke A, Mounier E, Goebel J, Loskutoff DJ, Konstantinides S (2003) Enhanced thrombosis in atherosclerosis-prone mice is associated with increased arterial expression of plasminogen activator inhibitor-1. Arterioscler Thromb Vasc Biol 23(11):2097–2103

    Article  PubMed  CAS  Google Scholar 

  155. Khoukaz HB, Ji Y, Braet DJ, Vadali M, Abdelhamid AA, Emal CD, Lawrence DA, Fay WP (2020) Drug targeting of plasminogen activator inhibitor-1 inhibits metabolic dysfunction and atherosclerosis in a murine model of metabolic syndrome. Arterioscler Thromb Vasc Biol 40(6):1479–1490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Zorio E, Gilabert-Estelles J, Espana F, Ramon LA, Cosin R, Estelles A (2008) Fibrinolysis: the key to new pathogenetic mechanisms. Curr Med Chem 15(9):923–929

    Article  CAS  PubMed  Google Scholar 

  157. Suehiro A, Wakabayashi I, Uchida K, Yamashita T, Yamamoto J (2012) Impaired spontaneous thrombolytic activity measured by global thrombosis test in males with metabolic syndrome. Thromb Res 129(4):499–501

    Article  CAS  PubMed  Google Scholar 

  158. Schneiderman J, Sawdey MS, Keeton MR, Bordin GM, Bernstein EF, Dilley RB, Loskutoff DJ (1992) Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. Proc Natl Acad Sci U S A 89(15):6998–7002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Sjoland H, Eitzman DT, Gordon D, Westrick R, Nabel EG, Ginsburg D (2000) Atherosclerosis progression in LDL receptor-deficient and apolipoprotein E-deficient mice is independent of genetic alterations in plasminogen activator inhibitor-1. Arterioscler Thromb Vasc Biol 20(3):846–852

    Article  CAS  PubMed  Google Scholar 

  160. Kaji H (2016) Adipose tissue-derived plasminogen activator inhibitor-1 function and regulation. Compr Physiol 6(4):1873–1896

    Article  PubMed  Google Scholar 

  161. Liu Y, Zhong Y, Chen H, Wang D, Wang M, Ou JS, Xia M (2017) Retinol-binding protein-dependent cholesterol uptake regulates macrophage foam cell formation and promotes atherosclerosis. Circulation 135(14):1339–1354

    Article  CAS  PubMed  Google Scholar 

  162. Kadoglou NP, Lambadiari V, Gastounioti A, Gkekas C, Giannakopoulos TG, Koulia K, Maratou E, Alepaki M, Kakisis J, Karakitsos P et al (2014) The relationship of novel adipokines, RBP4 and omentin-1, with carotid atherosclerosis severity and vulnerability. Atherosclerosis 235(2):606–612

    Article  CAS  PubMed  Google Scholar 

  163. Wu G, Li H, Zhou M, Fang Q, Bao Y, Xu A, Jia W (2014) Mechanism and clinical evidence of lipocalin-2 and adipocyte fatty acid-binding protein linking obesity and atherosclerosis. Diabetes Metab Res Rev 30(6):447–456

    Article  CAS  PubMed  Google Scholar 

  164. Mosialou I, Shikhel S, Luo N, Petropoulou PI, Panitsas K, Bisikirska B, Rothman NJ, Tenta R, Cariou B, Wargny M et al (2020) Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes. J Exp Med. https://doi.org/10.1084/jem.20191261

    Article  PubMed  PubMed Central  Google Scholar 

  165. Mosialou I, Shikhel S, Liu JM, Maurizi A, Luo N, He Z, Huang Y, Zong H, Friedman RA, Barasch J et al (2017) MC4R-dependent suppression of appetite by bone-derived lipocalin 2. Nature 543(7645):385–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Xiao Y, Xu A, Hui X, Zhou P, Li X, Zhong H, Tang W, Huang G, Zhou Z (2013) Circulating lipocalin-2 and retinol-binding protein 4 are associated with intima-media thickness and subclinical atherosclerosis in patients with type 2 diabetes. PLoS ONE 8(6):e66607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Shibata K, Sato K, Shirai R, Seki T, Okano T, Yamashita T, Koide A, Mitsuboshi M, Mori Y, Hirano T et al (2020) Lipocalin-2 exerts pro-atherosclerotic effects as evidenced by in vitro and in vivo experiments. Heart Vessels 35(7):1012–1024

    Article  PubMed  Google Scholar 

  168. Cook KS, Min HY, Johnson D, Chaplinsky RJ, Flier JS, Hunt CR, Spiegelman BM (1987) Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science 237(4813):402–405

    Article  CAS  PubMed  Google Scholar 

  169. Ohtsuki T, Satoh K, Shimizu T, Ikeda S, Kikuchi N, Satoh T, Kurosawa R, Nogi M, Sunamura S, Yaoita N et al (2019) Identification of adipsin as a novel prognostic biomarker in patients with coronary artery disease. J Am Heart Assoc 8(23):e013716

    Article  PubMed  PubMed Central  Google Scholar 

  170. Liu L, Chan M, Yu L, Wang W, Qiang L (2021) Adipsin deficiency does not impact atherosclerosis development in Ldlr(-/-) mice. Am J Physiol Endocrinol Metab 320(1):E87-e92

    Article  CAS  PubMed  Google Scholar 

  171. Madhur MS, Funt SA, Li L, Vinh A, Chen W, Lob HE, Iwakura Y, Blinder Y, Rahman A, Quyyumi AA et al (2011) Role of interleukin 17 in inflammation, atherosclerosis, and vascular function in apolipoprotein e-deficient mice. Arterioscler Thromb Vasc Biol 31(7):1565–1572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Smith E, Prasad KM, Butcher M, Dobrian A, Kolls JK, Ley K, Galkina E (2010) Blockade of interleukin-17A results in reduced atherosclerosis in apolipoprotein E-deficient mice. Circulation 121(15):1746–1755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. de la Paz S-M, Blanco-Favela F, Mora-Ruiz MD, Chavez-Rueda AK, Bernabe-Garcia M, Chavez-Sanchez L (2017) IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein. Lipids Health Dis 16(1):196

    Article  CAS  Google Scholar 

  174. Usui F, Kimura H, Ohshiro T, Tatsumi K, Kawashima A, Nishiyama A, Iwakura Y, Ishibashi S, Takahashi M (2012) Interleukin-17 deficiency reduced vascular inflammation and development of atherosclerosis in Western diet-induced apoE-deficient mice. Biochem Biophys Res Commun 420(1):72–77

    Article  CAS  PubMed  Google Scholar 

  175. Liuzzo G, Trotta F, Pedicino D (2013) Interleukin-17 in atherosclerosis and cardiovascular disease: the good, the bad, and the unknown. Eur Heart J 34(8):556–559

    Article  PubMed  Google Scholar 

  176. Ghoreschi K, Laurence A, Yang XP, Hirahara K, O’Shea JJ (2011) T helper 17 cell heterogeneity and pathogenicity in autoimmune disease. Trends Immunol 32(9):395–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Chen S, Crother TR, Arditi M (2010) Emerging role of IL-17 in atherosclerosis. J Innate Immun 2(4):325–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21(4):467–476

    Article  CAS  PubMed  Google Scholar 

  179. Hiramatsu-Ito M, Shibata R, Ohashi K, Uemura Y, Kanemura N, Kambara T, Enomoto T, Yuasa D, Matsuo K, Ito M et al (2016) Omentin attenuates atherosclerotic lesion formation in apolipoprotein E-deficient mice. Cardiovasc Res 110(1):107–117

    Article  CAS  PubMed  Google Scholar 

  180. Watanabe K, Watanabe R, Konii H, Shirai R, Sato K, Matsuyama TA, Ishibashi-Ueda H, Koba S, Kobayashi Y, Hirano T et al (2016) Counteractive effects of omentin-1 against atherogenesisdagger. Cardiovasc Res 110(1):118–128

    Article  CAS  PubMed  Google Scholar 

  181. Du Y, Ji Q, Cai L, Huang F, Lai Y, Liu Y, Yu J, Han B, Zhu E, Zhang J et al (2016) Association between omentin-1 expression in human epicardial adipose tissue and coronary atherosclerosis. Cardiovasc Diabetol 15:90

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Saely CH, Leiherer A, Muendlein A, Vonbank A, Rein P, Geiger K, Malin C, Drexel H (2016) High plasma omentin predicts cardiovascular events independently from the presence and extent of angiographically determined atherosclerosis. Atherosclerosis 244:38–43

    Article  CAS  PubMed  Google Scholar 

  183. Derwall M, Malhotra R, Lai CS, Beppu Y, Aikawa E, Seehra JS, Zapol WM, Bloch KD, Yu PB (2012) Inhibition of bone morphogenetic protein signaling reduces vascular calcification and atherosclerosis. Arterioscler Thromb Vasc Biol 32(3):613–622

    Article  CAS  PubMed  Google Scholar 

  184. Simoes Sato AY, Bub GL, Campos AH (2014) BMP-2 and -4 produced by vascular smooth muscle cells from atherosclerotic lesions induce monocyte chemotaxis through direct BMPRII activation. Atherosclerosis 235(1):45–55

    Article  CAS  PubMed  Google Scholar 

  185. Kim CW, Song H, Kumar S, Nam D, Kwon HS, Chang KH, Son DJ, Kang DW, Brodie SA, Weiss D et al (2013) Anti-inflammatory and antiatherogenic role of BMP receptor II in endothelial cells. Arterioscler Thromb Vasc Biol 33(6):1350–1359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Nencioni A, da Silva RF, Fraga-Silva RA, Steffens S, Fabre M, Bauer I, Caffa I, Magnone M, Sociali G, Quercioli A et al (2014) Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice. Thromb Haemost 111(2):308–322

    Article  CAS  PubMed  Google Scholar 

  187. Li S, Wang C, Li K, Li L, Tian M, Xie J, Yang M, Jia Y, He J, Gao L et al (2016) NAMPT knockdown attenuates atherosclerosis and promotes reverse cholesterol transport in ApoE KO mice with high-fat-induced insulin resistance. Sci Rep 6:26746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Bermudez B, Dahl TB, Medina I, Groeneweg M, Holm S, Paz SM, Rousch M, Otten J, Herias V, Varela LM et al (2017) leukocyte overexpression of intracellular NAMPT attenuates atherosclerosis by regulating PPARgamma-dependent monocyte differentiation and function. Arterioscler Thromb Vasc Biol 37(6):1157–1167

    Article  CAS  PubMed  Google Scholar 

  189. Aust G, Richter O, Rohm S, Kerner C, Hauss J, Kloting N, Ruschke K, Kovacs P, Youn BS, Bluher M (2009) Vaspin serum concentrations in patients with carotid stenosis. Atherosclerosis 204(1):262–266

    Article  CAS  PubMed  Google Scholar 

  190. Sato K, Shirai R, Yamaguchi M, Yamashita T, Shibata K, Okano T, Mori Y, Matsuyama TA, Ishibashi-Ueda H, Hirano T et al (2018) Anti-atherogenic effects of vaspin on human aortic smooth muscle cell/macrophage responses and hyperlipidemic mouse plaque phenotype. Int J Mol Sci. https://doi.org/10.3390/ijms19061732

    Article  PubMed  PubMed Central  Google Scholar 

  191. Rueda-Gotor J, Lopez-Mejias R, Remuzgo-Martinez S, Pulito-Cueto V, Corrales A, Lera-Gomez L, Portilla V, Gonzalez-Mazon I, Blanco R, Exposito R et al (2021) Vaspin in atherosclerotic disease and cardiovascular risk in axial spondyloarthritis: a genetic and serological study. Arthritis Res Ther 23(1):111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Basurto L, Gregory MA, Hernandez SB, Sanchez-Huerta L, Martinez AD, Manuel-Apolinar L, Avelar FJ, Alonso LAM, Sanchez-Arenas R (2019) Monocyte chemoattractant protein-1 (MCP-1) and fibroblast growth factor-21 (FGF-21) as biomarkers of subclinical atherosclerosis in women. Exp Gerontol 124:110624

    Article  CAS  PubMed  Google Scholar 

  193. Jia H, Cheng J, Zhou Q, Peng J, Pan Y, Han H (2018) Fibroblast growth factor 21 attenuates inflammation and oxidative stress in atherosclerotic rat via enhancing the Nrf1-ARE signaling pathway. Int J Clin Exp Pathol 11(3):1308–1317

    PubMed  PubMed Central  Google Scholar 

  194. Kokkinos J, Tang S, Rye KA, Ong KL (2017) The role of fibroblast growth factor 21 in atherosclerosis. Atherosclerosis 257:259–265

    Article  CAS  PubMed  Google Scholar 

  195. Li E, Wang T, Wang F, Wang T, Sun LQ, Li L, Niu SH, Zhang JY (2015) FGF21 protects against ox-LDL induced apoptosis through suppressing CHOP expression in THP1 macrophage derived foam cells. BMC Cardiovasc Disord 15:80

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  196. Lin Z, Pan X, Wu F, Ye D, Zhang Y, Wang Y, Jin L, Lian Q, Huang Y, Ding H et al (2015) Fibroblast growth factor 21 prevents atherosclerosis by suppression of hepatic sterol regulatory element-binding protein-2 and induction of adiponectin in mice. Circulation 131(21):1861–1871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Maeng HJ, Lee GY, Bae JH, Lim S (2020) Effect of fibroblast growth factor 21 on the development of atheromatous plaque and lipid metabolic profiles in an atherosclerosis-prone mouse model. Int J Mol Sci 21(18):6836

    Article  CAS  PubMed Central  Google Scholar 

  198. Pan ZC, Wang SP, Ou TT, Liu H, Ma JW, Wang WX, Fang WY, Qu XK, Zhang M (2017) A study on the expression of FGF-21 and NF-kappaB pathway in the tissues of atherosclerotic mice. Eur Rev Med Pharmacol Sci 21(3 Suppl):102–107

    PubMed  Google Scholar 

  199. Wu X, Lu Y, Fu K, Wang S, Zhao D, Peng H, Fan Q, Lu Y, Xin M, Liu J (2014) Impact of exogenous fibroblast growth factor 21 on atherosclerosis in apolipoprotein E deficient mice. Zhonghua Xin Xue Guan Bing Za Zhi 42(2):126–131

    PubMed  Google Scholar 

  200. Yafei S, Elsewy F, Youssef E, Ayman M, El-Shafei M (2019) Fibroblast growth factor 21 association with subclinical atherosclerosis and arterial stiffness in type 2 diabetes. Diabetes Metab Syndr 13(1):882–888

    Article  PubMed  Google Scholar 

  201. Yan X, Gou Z, Li Y, Wang Y, Zhu J, Xu G, Zhang Q (2018) Fibroblast growth factor 21 inhibits atherosclerosis in apoE-/- mice by ameliorating Fas-mediated apoptosis. Lipids Health Dis 17(1):203

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  202. Zhu W, Wang C, Liu L, Li Y, Li X, Cai J, Wang H (2014) Effects of fibroblast growth factor 21 on cell damage in vitro and atherosclerosis in vivo. Can J Physiol Pharmacol 92(11):927–935

    Article  CAS  PubMed  Google Scholar 

  203. Yu XH, Zhang DW, Zheng XL, Tang CK (2018) C1q tumor necrosis factor-related protein 9 in atherosclerosis: mechanistic insights and therapeutic potential. Atherosclerosis 276:109–116

    Article  CAS  PubMed  Google Scholar 

  204. Chiu CZ, Wang BW, Shyu KG (2015) Molecular regulation of the expression of leptin by hypoxia in human coronary artery smooth muscle cells. J Biomed Sci 22:5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Schroeter MR, Leifheit-Nestler M, Hubert A, Schumann B, Gluckermann R, Eschholz N, Kruger N, Lutz S, Hasenfuss G, Konstantinides S et al (2013) Leptin promotes neointima formation and smooth muscle cell proliferation via NADPH oxidase activation and signalling in caveolin-rich microdomains. Cardiovasc Res 99(3):555–565

    Article  CAS  PubMed  Google Scholar 

  206. Boord JB, Maeda K, Makowski L, Babaev VR, Fazio S, Linton MF, Hotamisligil GS (2004) Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice. Circulation 110(11):1492–1498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Coleman SL, Park YK, Lee JY (2011) Unsaturated fatty acids repress the expression of adipocyte fatty acid binding protein via the modulation of histone deacetylation in RAW 264.7 macrophages. Eur J Nutr 50(5):323–330

    Article  CAS  PubMed  Google Scholar 

  208. Hasan ST, Zingg JM, Kwan P, Noble T, Smith D, Meydani M (2014) Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice. Atherosclerosis 232(1):40–51

    Article  CAS  PubMed  Google Scholar 

  209. Hertzel AV, Xu H, Downey M, Kvalheim N, Bernlohr DA (2017) Fatty acid binding protein 4/aP2-dependent BLT1R expression and signaling. J Lipid Res 58(7):1354–1361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Krusinova E, Pelikanova T (2008) Fatty acid binding proteins in adipose tissue: a promising link between metabolic syndrome and atherosclerosis? Diabetes Res Clin Pract 82(Suppl 2):S127-134

    Article  CAS  PubMed  Google Scholar 

  211. Mankowska-Cyl A, Krintus M, Rajewski P, Sypniewska G (2013) A-FABP and its association with atherogenic risk profile and insulin resistance in young overweight and obese women. Biomark Med 7(5):723–730

    Article  CAS  PubMed  Google Scholar 

  212. Xiao Y, Xiao X, Xu A, Chen X, Tang W, Zhou Z (2018) Circulating adipocyte fatty acid-binding protein levels predict the development of subclinical atherosclerosis in type 2 diabetes. J Diabetes Compl 32(12):1100–1104

    Article  Google Scholar 

  213. Wang X, Chen L, Liu J, Yan T, Wu G, Xia Y, Zong G, Li F (2016) In vivo treatment of rat arterial adventitia with interleukin1beta induces intimal proliferation via the JAK2/STAT3 signaling pathway. Mol Med Rep 13(4):3451–3458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Roubille F, Busseuil D, Shi Y, Nachar W, Mihalache-Avram T, Mecteau M, Gillis MA, Brand G, Theberge-Julien G, Brodeur MR et al (2014) The interleukin-1beta modulator gevokizumab reduces neointimal proliferation and improves reendothelialization in a rat carotid denudation model. Atherosclerosis 236(2):277–285

    Article  CAS  PubMed  Google Scholar 

  215. Yan AT, Yan RT, Cushman M, Redheuil A, Tracy RP, Arnett DK, Rosen BD, McClelland RL, Bluemke DA, Lima JA (2010) Relationship of interleukin-6 with regional and global left-ventricular function in asymptomatic individuals without clinical cardiovascular disease: insights from the multi-ethnic study of atherosclerosis. Eur Heart J 31(7):875–882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Amersfoort J, Schaftenaar FH, Douna H, van Santbrink PJ, Kroner MJ, van Puijvelde GHM, Quax PHA, Kuiper J, Bot I (2018) Lipocalin-2 contributes to experimental atherosclerosis in a stage-dependent manner. Atherosclerosis 275:214–224

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Dr. Bingxiang Xu from Shanghai University of Sport for his participating in designing the frame of this manuscript.

Funding

This work was supported by Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, the research program of exercise and public health (0831) in Shanghai University of Sport, Shanghai higher education young teachers training funding program (A2-0213-22-0058-5) and the National Institutes of Health grants DK112943, DK128848, and HL087123 to L.Q.

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  1. Longhua Liu and Zunhan Shi have contributed equally to this work.

Authors and Affiliations

  1. School of Kinesiology, Shanghai University of Sport, Shanghai, People’s Republic of China

    Longhua Liu, Zunhan Shi, Xiaohui Ji, Wenqian Zhang & Jinwen Luan

  2. Department of Pharmacology, Columbia University, New York, NY, USA

    Tarik Zahr

  3. Department of Pathology and Cellular Biology and Naomi Berrie Diabetes Center, Columbia University, New York, NY, USA

    Li Qiang

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  1. Longhua Liu
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LL, ZS, XJ, WZ, JL, TZ, and LQ all contributed to the literature search, writing, and revising the manuscript. LL and LQ designed the frame of this manuscript. All authors contributed to this manuscript and approved the submitted version.

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Liu, L., Shi, Z., Ji, X. et al. Adipokines, adiposity, and atherosclerosis. Cell. Mol. Life Sci. 79, 272 (2022). https://doi.org/10.1007/s00018-022-04286-2

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