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Adipokine Dysregulation and Insulin Resistance with Atherosclerotic Vascular Disease: Metabolic Syndrome or Independent Sequelae?

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Abstract

Adipokine dysregulation and insulin resistance are two hallmark sequelae attributed to the current clinical definition of metabolic syndrome (MetS) that are also linked to atherosclerotic vascular disease. Here, we critically discuss the underlying pathophysiological mechanisms and the interplay between the two sequelae. Adipokine dysregulation is involved with decreased nitric oxide, vascular inflammation, and insulin resistance in itself to promote atherosclerosis. Insulin resistance is involved with endothelial dysfunction by direct and indirect mechanisms that also promote vascular inflammation and atherosclerosis. These mechanisms are discussed in atherosclerosis irrespective of MetS, and to evaluate the possibility of synergism in MetS. High retinol-binding protein-4 (RBP-4) and low cholesterol efflux in MetS may provide evidence of possible synergism and elevated atherosclerotic risk. An adverse adipokine panel that includes fetuin-A and adiponectin can potentially assess atherosclerotic risk in even those without MetS. Genetic possibilities may exist in atherosclerotic vascular diseases secondary to insulin resistance.

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References

  1. Kahn, R. (2006). The metabolic syndrome: Time for a critical appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes: Response to Citrome et al., Giugliano and Esposito, Cheta, and Psaty et al. Diabetes Care, 29(1), 177–178. https://doi.org/10.2337/diacare.29.1.177-a.

    Article  Google Scholar 

  2. Engin, A. (2017). The definition and prevalence of obesity and metabolic syndrome. Obesity and Lipotoxicity Advances in Experimental Medicine and Biology, 1–17. https://doi.org/10.1007/978-3-319-48382-5_1.

    Chapter  Google Scholar 

  3. Thorn, L. M., Forsblom, C., Waden, J., et al. (2009). Metabolic syndrome as a risk factor for cardiovascular disease, mortality, and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care, 32(5), 950–952. https://doi.org/10.2337/dc08-2022.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Khan, Q. A., Sola, S., & Khan, B. V. (2006). The metabolic syndrome: Inflammation and endothelial dysfunction. Hospital Physician, 42, 26–37.

    Google Scholar 

  5. Preventing Chronic Disease. Centers for Disease Control and Prevention. https://www.cdc.gov/pcd/issues/2017/16_0287.htm. Published September 20, 2017. Accessed September 2, 2018.

  6. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595–1607.

    Article  CAS  Google Scholar 

  7. Haller, H. (1977). Epidemiology and associated risk factors of hyperlipoproteinemia. Z Gesamte Inn Med, 32, 124–128.

    CAS  PubMed  Google Scholar 

  8. Singer, P. (1977). Diagnosis of primary hyperlipoproteinemias. Z Gesamte Inn Med, 32, 129–133.

    CAS  PubMed  Google Scholar 

  9. Phillips, G. B. (1977). Relationship between serum sex hormones and glucose, insulin, and lipid abnormalities in men with myocardial infarction. Proceedings of the National Academy of Sciences of the United States of America, 74, 1729–1733.

    Article  CAS  Google Scholar 

  10. Third Report of the National Cholesterol Education Program (NCEP). (2002). Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation, 106, 3143–3421.

    Article  Google Scholar 

  11. Alberti, K. G., Eckel, R. H., Grundy, S. M., et al. (2010). Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Obesity and Metabolism, (1), 63. https://doi.org/10.14341/2071-8713-5281.

    Article  Google Scholar 

  12. Cull, C. A., Jensen, C. C., Retnakaran, R., & Holman, R. R. (2007). Impact of the metabolic syndrome on macrovascular and microvascular outcomes in type 2 diabetes mellitus: United Kingdom Prospective Diabetes Study 78. Circulation, 116(19), 2119–2126. https://doi.org/10.1161/circulationaha.107.733428.

    Article  PubMed  Google Scholar 

  13. Maury, E., & Brichard, S. (2010). Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Molecular and Cellular Endocrinology, 314(1), 1–16. https://doi.org/10.1016/j.mce.2009.07.031.

    Article  CAS  PubMed  Google Scholar 

  14. Mohammadi, M., Gozashti, M. H., Aghadavood, M., Mehdizadeh, M. R., & Hayatbakhsh, M. M. (2017). Clinical significance of serum IL-6 and TNF-α levels in patients with metabolic syndrome. Reports of Biochemistry & Molecular Biology, 6(1), 74–79.

    CAS  Google Scholar 

  15. Skoog, T. (2002). Plasma tumour necrosis factor-α and early carotid atherosclerosis in healthy middle-aged men. European Heart Journal, 23(5), 376–383. https://doi.org/10.1053/euhj.2001.2805.

    Article  CAS  PubMed  Google Scholar 

  16. Ohta, H., Wada, H., Niwa, T., et al. (2005). Disruption of tumor necrosis factor-α gene diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis, 180(1), 11–17. https://doi.org/10.1016/j.atherosclerosis.2004.11.016.

    Article  CAS  PubMed  Google Scholar 

  17. Martinovic, I., Abegunewardene, N., Seul, M., et al. (2005). Elevated monocyte chemoattractant protein-1 serum levels in patients at risk for coronary artery disease. Circulation Journal, 69(12), 1484–1489. https://doi.org/10.1253/circj.69.1484.

    Article  CAS  PubMed  Google Scholar 

  18. Alessi, M.-C., Poggi, M., & Juhan-Vague, I. (2007). Plasminogen activator inhibitor-1, adipose tissue and insulin resistance. Current Opinion in Lipidology, 18(3), 240–245. https://doi.org/10.1097/mol.0b013e32814e6d29.

    Article  CAS  PubMed  Google Scholar 

  19. Scheer, F. A., & Shea, S. A. (2014). Human circadian system causes a morning peak in prothrombotic plasminogen activator inhibitor-1 (PAI-1) independent of the sleep/wake cycle. Blood, 123, 590–593.

    Article  CAS  Google Scholar 

  20. Kodaman, N., Aldrich, M. C., Sobota, R., et al. (2016). Plasminogen activator Inhibitor-1 and diagnosis of the metabolic syndrome in a West African population. Journal of the American Heart Association, 5(10). https://doi.org/10.1161/jaha.116.003867.

  21. Alessi, M. C., & Juhan-Vague, I. (2004). Contribution of PAI-1 in cardiovascular pathology. Archives des Maladies du Coeur et des Vaisseaux, 97, 673–678.

    CAS  PubMed  Google Scholar 

  22. Alessi, M. C., & Juhan-Vague, I. (2006). PAI-1 and the metabolic syndrome: Links, causes, and consequences. Arteriosclerosis, Thrombosis, and Vascular Biology, 26, 2200–2207.

    Article  CAS  Google Scholar 

  23. Zarins, C. K., Giddens, D. P., Bharadvaj, B. K., Sottiurai, V. S., Mabon, R. F., & Glagov, S. (1983). Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circulation Research, 53(4), 502–514. https://doi.org/10.1161/01.res.53.4.502.

    Article  CAS  PubMed  Google Scholar 

  24. Gnasso, A., Irace, C., Carallo, C., et al. (1997). In vivo association between low wall shear stress and plaque in subjects with asymmetrical carotid atherosclerosis. Stroke., 28(5), 993–998. https://doi.org/10.1161/01.str.28.5.993.

    Article  CAS  PubMed  Google Scholar 

  25. Ku, D. N., Giddens, D. P., Zarins, C. K., & Glagov, S. (1985). Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis, Thrombosis, and Vascular Biology, 5(3), 293–302. https://doi.org/10.1161/01.atv.5.3.293.

    Article  CAS  Google Scholar 

  26. Yang, J., Cho, K., Kim, J., et al. (2014). Wall shear stress in hypertensive patients is associated with carotid vascular deformation assessed by speckle tracking strain imaging. Clinical Hypertension, 20(1), 10. https://doi.org/10.1186/2056-5909-20-10.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Harrison, D. G., Guzik, T. J., Goronzy, J., & Weyand, C. (2008). Is hypertension an immunologic disease? Current Cardiology Reports, 10(6), 464–469. https://doi.org/10.1007/s11886-008-0073-6.

    Article  PubMed  Google Scholar 

  28. Yvan-Charvet, L., & Quignard-Boulangé, A. (2011). Role of adipose tissue renin–angiotensin system in metabolic and inflammatory diseases associated with obesity. Kidney International, 79(2), 162–168. https://doi.org/10.1038/ki.2010.391.

    Article  CAS  PubMed  Google Scholar 

  29. Swirski, F. K., Nahrendorf, M., Etzrodt, M., et al. (2009). Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science, 325(5940), 612–616. https://doi.org/10.1126/science.1175202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fukuda, D., Sata, M., Ishizaka, N., & Nagai, R. (2007). Critical role of bone marrow angiotensin II type 1 receptor in the pathogenesis of atherosclerosis in apolipoprotein E deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(1), 90–96. https://doi.org/10.1161/atvbaha.107.152363.

    Article  PubMed  Google Scholar 

  31. Ishibashi, M. (2004). Bone marrow-derived monocyte chemoattractant protein-1 receptor CCR2 is critical in angiotensin II-induced acceleration of atherosclerosis and aneurysm formation in hypercholesterolemic mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 24(11). https://doi.org/10.1161/01.atv.0000143384.69170.2d.

  32. Angiotensin II-mediated vasoconstriction of the visceral adipose tissue vasculature is linked to systemic hypertension in obesity. The FASEB Journal. https://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.684.6. Accessed September 4, 2018.

  33. Chun, H. J., Ali, Z. A., Kojima, Y., et al. (2008). Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis. Journal of Clinical Investigation. https://doi.org/10.1172/jci34871.

  34. Mutlak, S. S., Ali, V. S., & Hussein, R. M. (2018). Apelin and some biomarkers in females with metabolic syndrome. Biomedical and Pharmacology Journal, 11(1), 247–253. https://doi.org/10.13005/bpj/1369.

    Article  CAS  Google Scholar 

  35. Angelova, P., Kamenov, Z., & Tsakova, A. (2014). Apelin and testosterone levels in men with metabolic syndrome. Open Journal of Endocrine and Metabolic Diseases, 04(02), 35–43. https://doi.org/10.4236/ojemd.2014.42004.

    Article  CAS  Google Scholar 

  36. Katugampola, S. D., Maguire, J. J., Matthewson, S. R., & Davenport, A. P. (2001). [125I]-(Pyr1)Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man. British Journal of Pharmacology, 132(6), 1255–1260. https://doi.org/10.1038/sj.bjp.0703939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kuba, K., Zhang, L., Imai, Y., et al. (2007). Impaired heart contractility in Apelin gene deficient mice associated with aging and pressure overload. Circulation Research, 101(4). https://doi.org/10.1161/circresaha.107.158659.

  38. Yue, P., Jin, H., Aillaud, M., et al. (2010). Apelin is necessary for the maintenance of insulin sensitivity. American Journal of Physiology. Endocrinology and Metabolism, 298(1). https://doi.org/10.1152/ajpendo.00385.2009.

    Article  CAS  Google Scholar 

  39. Zachariah, J. P., Quiroz, R., Nelson, K. P., et al. (2017). Prospective relation of circulating adipokines to incident metabolic syndrome: The Framingham Heart Study. Journal of the American Heart Association, 6(7). https://doi.org/10.1161/jaha.116.004974.

  40. Yang, Q., Graham, T. E., Mody, N., et al. (2005). Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature, 436(7049), 356–362. https://doi.org/10.1038/nature03711.

    Article  CAS  PubMed  Google Scholar 

  41. Rauth, G., Poschke, O., Fink, E., Eulitz, M., Tippmer, S., Kellerer, M., Haring, H. U., Nawratil, P., Haasemann, M., Jahnen-Dechent, W., & Muller-Esterl, W. (1992). The nucleotide and partial amino acid sequences of rat fetuin. Identity with the natural tyrosine kinase inhibitor of the rat insulin receptor. European Journal of Biochemistry, 204, 523–529.

    Article  CAS  Google Scholar 

  42. Weikert, C., Stefan, N., Schulze, M. B., Pischon, T., Berger, K., Joost, H. G., Haring, H. U., Boeing, H., & Fritsche, A. (2008). Plasma fetuin-A levels and the risk of myocardial infarction and ischemic stroke. Circulation, 118, 2555–2562.

    Article  CAS  Google Scholar 

  43. Ruan, H., & Dong, L. Q. (2016). Adiponectin signaling and function in insulin target tissues. Journal of Molecular Cell Biology, 8(2), 101–109. https://doi.org/10.1093/jmcb/mjw014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang, X., Chen, Q., Pu, H., et al. (2016). Adiponectin improves NF-κB-mediated inflammation and abates atherosclerosis progression in apolipoprotein E-deficient mice. Lipids in Health and Disease, 15(1). https://doi.org/10.1186/s12944-016-0202-y.

  45. Li, R., Wang, W.-Q., Zhang, H., et al. (2007). Adiponectin improves endothelial function in hyperlipidemic rats by reducing oxidative/nitrative stress and differential regulation of eNOS/iNOS activity. American Journal of Physiology. Endocrinology and Metabolism, 293(6). https://doi.org/10.1152/ajpendo.00462.2007.

    Article  CAS  Google Scholar 

  46. Ouchi, N., Kihara, S., Arita, Y., et al. (1999). Novel modulator for endothelial adhesion molecules: Adipocyte-derived plasma protein adiponectin. Circulation, 100(25), 2473–2476. https://doi.org/10.1161/01.cir.100.25.2473.

    Article  CAS  PubMed  Google Scholar 

  47. Arita, Y. (2002). Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation, 105(24), 2893–2898. https://doi.org/10.1161/01.cir.0000018622.84402.ff.

    Article  CAS  PubMed  Google Scholar 

  48. Martín-Romero, C., Santos-Alvarez, J., Goberna, R., & Sánchez-Margalet, V. (2000). Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cellular Immunology, 199(1), 15–24. https://doi.org/10.1006/cimm.1999.1594.

    Article  CAS  PubMed  Google Scholar 

  49. Oda, A., Taniguchi, T., Takahash, A., et al. (2001). Leptin stimulates rat aortic smooth muscle cell proliferation and migration. The Kobe Journal of Medical Sciences, 47, 141–150. https://doi.org/10.1016/s0021-9150(97)89646-3.

    Article  CAS  PubMed  Google Scholar 

  50. Kraemer, R., Nguyen, H., March, K. L., & Hempstead, B. (1999). NGF activates similar intracellular signaling pathways in vascular smooth muscle cells as PDGF-BB but elicits different biological responses. Arteriosclerosis, Thrombosis, and Vascular Biology, 19(4), 1041–1050. https://doi.org/10.1161/01.atv.19.4.1041.

    Article  CAS  PubMed  Google Scholar 

  51. Maingrette, F., & Renier, G. (2003). Leptin increases lipoprotein lipase secretion by macrophages: Involvement of oxidative stress and protein kinase C. Diabetes., 52(8), 2121–2128. https://doi.org/10.2337/diabetes.52.8.2121.

    Article  CAS  PubMed  Google Scholar 

  52. Yang, H., Guo, W., Li, J., et al. (2017). Leptin concentration and risk of coronary heart disease and stroke: A systematic review and meta-analysis. PLoS One, 12(3). https://doi.org/10.1371/journal.pone.0166360.

    Article  Google Scholar 

  53. Su, Y., Liu, X.-M., Sun, Y.-M., Wang, Y.-Y., Luan, Y., & Wu, Y. (2008). Endothelial dysfunction in impaired fasting glycemia, impaired glucose tolerance, and type 2 diabetes mellitus. The American Journal of Cardiology, 102(4), 497–498. https://doi.org/10.1016/j.amjcard.2008.03.087.

    Article  CAS  PubMed  Google Scholar 

  54. Kolovou, G. D. (2005). Pathophysiology of dyslipidaemia in the metabolic syndrome. Postgraduate Medical Journal, 81(956), 358–366. https://doi.org/10.1136/pgmj.2004.025601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Janus, A., Szahidewicz-Krupska, E., Mazur, G., & Doroszko, A. (2016). Insulin resistance and endothelial dysfunction constitute a common therapeutic target in cardiometabolic disorders. Mediators of Inflammation, 2016, 3634948. https://doi.org/10.1155/2016/3634948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Davignon, J. (2004). Role of endothelial dysfunction in atherosclerosis. Circulation, 109(23_suppl_1). https://doi.org/10.1161/01.cir.0000131515.03336.f8.

    Google Scholar 

  57. Deedwania, P. C. (2003). Mechanisms of endothelial dysfunction in the metabolic syndrome. Current Diabetes Reports, 3(4), 289–292. https://doi.org/10.1007/s11892-003-0019-8.

    Article  PubMed  Google Scholar 

  58. Kahn, N. N., Acharya, K., & Bhattachary, S. (2000). Nitric oxide: The “second messenger” of insulin. IUBMB Life (International Union of Biochemistry and Molecular Biology: Life), 49(5), 441–450. https://doi.org/10.1080/152165400410308.

    Article  CAS  Google Scholar 

  59. Lee, S. K., Khambhati, K., Bhargava, A., Engels, M. C., Sandesara, P. B., & Quyyumi, A. A. (2017). Endothelial dysfunction and metabolic syndrome. Hypertens Journal, 3(2), 72–80.

    Article  Google Scholar 

  60. Shinozaki, K., Hirayama, A., Nishio, Y., et al. (2001). Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress. Journal of the American College of Cardiology, 38(7), 1821–1828. https://doi.org/10.1016/s0735-1097(01)01659-x.

    Article  CAS  PubMed  Google Scholar 

  61. Shinozaki, K., Nishio, Y., Okamura, T., et al. (2000). Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in aortas of insulin-resistant rats. Circulation Research, 87, 566–573.

    Article  CAS  Google Scholar 

  62. Prato, S. D. (2009). Role of glucotoxicity and lipotoxicity in the pathophysiology of type 2 diabetes mellitus and emerging treatment strategies. Diabetic Medicine, 26(12), 1185–1192. https://doi.org/10.1111/j.1464-5491.2009.02847.x.

    Article  CAS  PubMed  Google Scholar 

  63. Musicki, B., Kramer, M. F., Becker, R. E., & Burnett, A. L. (2005). Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction. Proceedings of the National Academy of Sciences, 102(33), 11870–11875. https://doi.org/10.1073/pnas.0502488102.

    Article  CAS  Google Scholar 

  64. Hançer, N. J., Qiu, W., Cherella, C., Li, Y., Copps, K. D., & White, M. F. (2014). Insulin and metabolic stress stimulate multisite serine/threonine phosphorylation of insulin receptor substrate 1 and inhibit tyrosine phosphorylation. Journal of Biological Chemistry, 289(18), 12467–12484. https://doi.org/10.1074/jbc.m114.554162.

    Article  PubMed  Google Scholar 

  65. Puyvelde, K. V., Mets, T., Njemini, R., Beyer, I., & Bautmans, I. (2014). Effect of advanced glycation end product intake on inflammation and aging: A systematic review. Nutrition Reviews, 72(10), 638–650. https://doi.org/10.1111/nure.12141.

    Article  PubMed  Google Scholar 

  66. Gonzalez-Sanchez, J. L., Martinez-Larrad, M. T., Saez, M. E., Zabena, C., Martinez-Calatrava, M. J., & Serrano-Rios, M. (2006). Endothelial nitric oxide synthase haplotypes are associated with features of metabolic syndrome. Clinical Chemistry, 53(1), 91–97. https://doi.org/10.1373/clinchem.2006.075176.

    Article  PubMed  Google Scholar 

  67. Ertunc, M. E., & Hotamisligil, G. S. (2016). Lipid signaling and lipotoxicity in metaflammation: Indications for metabolic disease pathogenesis and treatment. Journal of Lipid Research, 57(12), 2099–2114. https://doi.org/10.1194/jlr.r066514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wende, A. R., Symons, J. D., & Abel, E. D. (2012). Mechanisms of lipotoxicity in the cardiovascular system. Current Hypertension Reports, 14(6), 517–531. https://doi.org/10.1007/s11906-012-0307-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Li, H., Li, H., Bao, Y., Zhang, X., & Yu, Y. (2011). Free fatty acids induce endothelial dysfunction and activate protein kinase C and nuclear factor-κB pathway in rat aorta. International Journal of Cardiology, 152(2), 218–224. https://doi.org/10.1016/j.ijcard.2010.07.019.

    Article  PubMed  Google Scholar 

  70. Inoguchi, T., Li, P., Umeda, F., et al. (2000). High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes, 49(11), 1939–1945. https://doi.org/10.2337/diabetes.49.11.1939.

    Article  CAS  PubMed  Google Scholar 

  71. Hsueh, W. A., & Quiñones, M. J. (2003). Role of endothelial dysfunction in insulin resistance. The American Journal of Cardiology, 92(4), 10–17. https://doi.org/10.1016/s0002-9149(03)00611-8.

    Article  Google Scholar 

  72. Ferri, C., Pittoni, V., Piccoli, A., et al. (1995). Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo. The Journal of Clinical Endocrinology & Metabolism, 80(3), 829–835. https://doi.org/10.1210/jc.80.3.829.

    Article  CAS  Google Scholar 

  73. Mathew, M., Tay, E., & Cusi, K. (2010). Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects. Cardiovascular Diabetology, 9(1), 9. https://doi.org/10.1186/1475-2840-9-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Sihvola, R. K., Pulkkinen, V. P., Koskinen, P. K., & Lemström, K. B. (2002). Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis. Journal of the American College of Cardiology, 39(4), 710–717. https://doi.org/10.1016/s0735-1097(01)01782-x.

    Article  CAS  PubMed  Google Scholar 

  75. Goto, K., & Miyauchi, T. (2003). New expansion of endothelin research: Perspectives for clinical application of endothelin-receptor antagonists. Folia Pharmacologica Japonica, 121(2), 91–101. https://doi.org/10.1254/fpj.121.91.

    Article  CAS  PubMed  Google Scholar 

  76. Lupattelli, G., Marchesi, S., Lombardini, R., et al. (2003). Mechanisms of high-density lipoprotein cholesterol effects on the endothelial function in hyperlipemia. Metabolism, 52(9), 1191–1195. https://doi.org/10.1016/s0026-0495(03)00157-4.

    Article  CAS  PubMed  Google Scholar 

  77. Wang, W., Hein, T. W., Zhang, C., Zawieja, D. C., Liao, J. C., & Kuo, L. (2010). Oxidized low-density lipoprotein inhibits nitric oxide-mediated coronary arteriolar dilation by up-regulating endothelial arginase I. Microcirculation, 18(1), 36–45. https://doi.org/10.1111/j.1549-8719.2010.00066.x.

    Article  CAS  Google Scholar 

  78. Wen, C. P., Chan, H. T., Tsai, M. K., Cheng, T. Y., Chung, W. S., Chang, Y. C., Hsu, H. L., Tsai, S. P., Tsao, C. K., Man Wai, J. P., & Hsu, C. C. (2011). Attributable mortality burden of metabolic syndrome: Comparison with its individual components. European Journal of Cardiovascular Prevention and Rehabilitation, 18, 561–573.

    Article  Google Scholar 

  79. Samaras, K., Crawford, J., Baune, B. T., Campbell, L. V., Smith, E., Lux, O., Brodaty, H., Trollor, J. N., & Sachdev, P. (2012). The value of the metabolic syndrome concept in elderly adults: Is it worth less than the sum of its parts? Journal of the American Geriatrics Society, 60, 1734–1741.

    Article  Google Scholar 

  80. Godsland, I. F., Lecamwasam, K., & Johnston, D. G. (2011). A systematic evaluation of the insulin resistance syndrome as an independent risk factor for cardiovascular disease mortality and derivation of a clinical index. Metabolism, 60, 1442–1448.

    Article  CAS  Google Scholar 

  81. Hung, J., Mcquillan, B. M., Thompson, P. L., & Beilby, J. P. (2008). Circulating adiponectin levels associate with inflammatory markers, insulin resistance and metabolic syndrome independent of obesity. International Journal of Obesity, 32(5), 772–779. https://doi.org/10.1038/sj.ijo.0803793.

    Article  CAS  PubMed  Google Scholar 

  82. Gall, J., Frisdal, E., Bittar, R., et al. (2016). Association of cholesterol efflux capacity with clinical features of metabolic syndrome: Relevance to atherosclerosis. Journal of the American Heart Association, 5(12). https://doi.org/10.1161/jaha.116.004808.

  83. Ohashi, K., et al. (2004). Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery disease. Journal of the American College of Cardiology, 43, 1195–1200.

    Article  CAS  Google Scholar 

  84. Virtue, A., Johnson, C., Lopez-Pastraña, J., et al. (2016). MicroRNA-155 deficiency leads to decreased atherosclerosis, increased white adipose tissue obesity, and non-alcoholic fatty liver disease. Journal of Biological Chemistry, 292(4), 1267–1287. https://doi.org/10.1074/jbc.m116.739839.

    Article  PubMed  Google Scholar 

  85. Mirra, P., Nigro, C., Prevenzano, I., et al. (2017). The role of miR-190a in methylglyoxal-induced insulin resistance in endothelial cells. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1863(2), 440–449. https://doi.org/10.1016/j.bbadis.2016.11.018.

    Article  CAS  Google Scholar 

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Funding

The research work of DK Agrawal is supported by research grants R01HL120659 and R01HL144125 from the National Institutes of Health, USA. The content of this review article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Clinical & Translational Science, The Peekie Nash Carpenter Endowed Chair in Medicine, Creighton University School of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE, 68178, USA

    Mohan Satish & Devendra K. Agrawal

  2. Department of Family Medicine, Creighton University School of Medicine, Omaha, NE, 68178, USA

    Shailendra K. Saxena

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  1. Mohan Satish
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  2. Shailendra K. Saxena
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  3. Devendra K. Agrawal
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Correspondence to Devendra K. Agrawal.

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All authors have read the journal’s policy on disclosure of potential conflicts of interest. Author C has received grants from the National Institutes of Health, State of Nebraska, and Dialysis Clinic Inc. Other authors have no other relevant affiliations or financial or non-financial involvement with any organization or entity with financial or non-financial interest or conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Author A (MS) declares that he has no conflict of interest. Author B (SKS) declares that he has no conflict of interest. Author C (DKA) declares that he has no conflict of interest.

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Satish, M., Saxena, S.K. & Agrawal, D.K. Adipokine Dysregulation and Insulin Resistance with Atherosclerotic Vascular Disease: Metabolic Syndrome or Independent Sequelae?. J. of Cardiovasc. Trans. Res. 12, 415–424 (2019). https://doi.org/10.1007/s12265-019-09879-0

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