Advertisement

Therapeutic targets for endothelial dysfunction in vascular diseases

  • Diem Thi Ngoc Huynh
  • Kyung-Sun HeoEmail author
Review
  • 81 Downloads

Abstract

Vascular endothelial cells are located on the surface of the blood vessels. It has been recognized as an important barrier to the regulation of vascular homeostasis by regulating the blood flow of micro- or macrovascular vessels. Indeed, endothelial dysfunction is an initial stage of vascular diseases and is an important prognostic indicator of cardiovascular and metabolic diseases such as atherosclerosis, hypertension, heart failure, or diabetes. Therefore, in order to develop therapeutic targets for vascular diseases, it is important to understand the key factors involved in maintaining endothelial function and the signaling pathways affecting endothelial dysfunction. The purpose of this review is to describe the function and underlying signaling pathway of oxidative stress, inflammatory factors, shear stress, and epigenetic factors in endothelial dysfunction, and introduce recent therapeutic targets for the treatment of cardiovascular diseases.

Keywords

Atherosclerosis Endothelial dysfunction Epigenetic factors Inflammation Oxidative stress Shear stress 

Notes

Acknowledgements

This research was supported by National Research Foundation of Korea (KNRF-2016232004 and -2019025901).

Compliance with ethical standards

Conflict of interest

None.

References

  1. Akaike M, Che W, Marmarosh NL, Ohta S, Osawa M, Ding B, Berk BC, Yan C, Abe J (2004) The hinge-helix 1 region of peroxisome proliferator-activated receptor gamma1 (PPARgamma1) mediates interaction with extracellular signal-regulated kinase 5 and PPARgamma1 transcriptional activation: involvement in flow-induced PPARgamma activation in endothelial cells. Mol Cell Biol 24(19):8691–8704.  https://doi.org/10.1128/mcb.24.19.8691-8704.2004 Google Scholar
  2. Ali L, Schnitzler JG, Kroon J (2018) Metabolism: the road to inflammation and atherosclerosis. Curr Opin Lipidol 29(6):474–480.  https://doi.org/10.1097/mol.0000000000000550 Google Scholar
  3. Bai J, Zhang N, Hua Y, Wang B, Ling L, Ferro A, Xu B (2013) Metformin inhibits angiotensin II-induced differentiation of cardiac fibroblasts into myofibroblasts. PLoS ONE 8(9):e72120.  https://doi.org/10.1371/journal.pone.0072120 Google Scholar
  4. Binesh A, Devaraj SN, Halagowder D (2019) Molecular interaction of NFkappaB and NICD in monocyte-macrophage differentiation is a target for intervention in atherosclerosis. J Cell Physiol 234(5):7040–7050.  https://doi.org/10.1002/jcp.27458 Google Scholar
  5. Boon RA, Horrevoets AJ (2009) Key transcriptional regulators of the vasoprotective effects of shear stress. Hamostaseologie 29(1):39–40, 41–33Google Scholar
  6. Breton-Romero R, Gonzalez de Orduna C, Romero N, Sánchez-Gómez FJ, de Álvaro C, Porras A, Rodríguez-Pascual F, Laranjinha J, Radi R, Lamas S (2012) Critical role of hydrogen peroxide signaling in the sequential activation of p38 MAPK and eNOS in laminar shear stress. Free Radic Biol Med 52(6):1093–1100.  https://doi.org/10.1016/j.freeradbiomed.2011.12.026 Google Scholar
  7. Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87(10):840–844Google Scholar
  8. Cai Y, Sukhova GK, Wong HK, Xu A, Tergaonkar V, Vanhoutte PM, Tang EHC (2015) Rap1 induces cytokine production in pro-inflammatory macrophages through NFkappaB signaling and is highly expressed in human atherosclerotic lesions. Cell Cycle 14(22):3580–3592.  https://doi.org/10.1080/15384101.2015.1100771 Google Scholar
  9. Chen W, Bacanamwo M, Harrison DG (2008) Activation of p300 histone acetyltransferase activity is an early endothelial response to laminar shear stress and is essential for stimulation of endothelial nitric-oxide synthase mRNA transcription. J Biol Chem 283(24):16293–16298.  https://doi.org/10.1074/jbc.m801803200 Google Scholar
  10. Chen Z, Peng IC, Cui X, Li YS, Chien S, Shyy JY (2010) Shear stress, SIRT1, and vascular homeostasis. Proc Natl Acad Sci USA 107(22):10268–10273.  https://doi.org/10.1073/pnas.1003833107 Google Scholar
  11. Chen Q, Wang Q, Zhu J, Xiao Q, Zhang L (2018) Reactive oxygen species: key regulators in vascular health and diseases. Br J Pharmacol 175(8):1279–1292.  https://doi.org/10.1111/bph.13828 Google Scholar
  12. Cheng Z, Jiang X, Kruger WD, Praticò D, Gupta S, Mallilankaraman K, Madesh M, Schafer AI, Durante W, Yang X, Wang H (2011) Hyperhomocysteinemia impairs endothelium-derived hyperpolarizing factor-mediated vasorelaxation in transgenic cystathionine beta synthase-deficient mice. Blood 118(7):1998–2006.  https://doi.org/10.1182/blood-2011-01-333310 Google Scholar
  13. Chiste RC, Freitas M, Mercadante AZ, Fernandes E (2015) Superoxide anion radical: generation and detection in cellular and non-cellular systems. Curr Med Chem 22(37):4234–4256Google Scholar
  14. Das S, Zhang E, Senapati P, Amaram V, Reddy MA, Stapleton K, Leung A, Lanting L, Wang M, Chen Z, Kato M, Oh HJ, Guo Q, Zhang X, Zhang B, Zhang H, Zhao Q, Wang W, Wu Y, Natarajan R (2018) A novel angiotensin II-induced long noncoding RNA giver regulates oxidative stress, inflammation, and proliferation in vascular smooth muscle cells. Circ Res 123(12):1298–1312.  https://doi.org/10.1161/circresaha.118.313207 Google Scholar
  15. De Silva TM, Li Y, Kinzenbaw DA, Sigmund CD, Faraci FM (2018) Endothelial PPARgamma (peroxisome proliferator-activated receptor-gamma) is essential for preventing endothelial dysfunction with aging. Hypertension 72(1):227–234.  https://doi.org/10.1161/hypertensionaha.117.10799 Google Scholar
  16. Dunn J, Qiu H, Kim S, Jjingo D, Hoffman R, Kim CW, Jang I, Son DJ, Kim D, Pan C, Fan Y, Jordan IK, Jo H (2014) Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis. J Clin Investig 124(7):3187–3199.  https://doi.org/10.1172/jci74792 Google Scholar
  17. Elia L, Condorelli G (2019) The involvement of epigenetics in vascular disease development. Int J Biochem Cell Biol 107:27–31.  https://doi.org/10.1016/j.biocel.2018.12.005 Google Scholar
  18. Fan W, Fang R, Wu X, Liu J, Feng M, Dai G, Chen G, Wu G (2015) Shear-sensitive microRNA-34a modulates flow-dependent regulation of endothelial inflammation. J Cell Sci 128(1):70–80.  https://doi.org/10.1242/jcs.154252 Google Scholar
  19. Fang Y, Shi C, Manduchi E, Civelek M, Davies PF (2010) MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci USA 107(30):13450–13455.  https://doi.org/10.1073/pnas.1002120107 Google Scholar
  20. Forstermann U, Xia N, Li H (2017) Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res 120(4):713–735.  https://doi.org/10.1161/circresaha.116.309326 Google Scholar
  21. Foryst-Ludwig A, Hartge M, Clemenz M, Sprang C, Heß K, Marx N, Unger T, Kintscher U (2010) PPARgamma activation attenuates T-lymphocyte-dependent inflammation of adipose tissue and development of insulin resistance in obese mice. Cardiovasc Diabetol 9:64.  https://doi.org/10.1186/1475-2840-9-64 Google Scholar
  22. Fraineau S, Palii CG, Allan DS, Brand M (2015) Epigenetic regulation of endothelial-cell-mediated vascular repair. FEBS J 282(9):1605–1629.  https://doi.org/10.1111/febs.13183 Google Scholar
  23. Gimbrone MA Jr, Garcia-Cardena G (2016) Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 118(4):620–636.  https://doi.org/10.1161/circresaha.115.306301 Google Scholar
  24. Godo S, Shimokawa H (2017) Divergent roles of endothelial nitric oxide synthases system in maintaining cardiovascular homeostasis. Free Radic Biol Med 109:4–10.  https://doi.org/10.1016/j.freeradbiomed.2016.12.019 Google Scholar
  25. Green JP, Souilhol C, Xanthis I, Martinez-Campesino L, Bowden NP, Evans PC, Wilson HL (2018) Atheroprone flow activates inflammation via endothelial ATP-dependent P2X7-p38 signalling. Cardiovasc Res 114(2):324–335.  https://doi.org/10.1093/cvr/cvx213 Google Scholar
  26. Heo KS, Lee H, Nigro P, Thomas T, Le N-T, Chang E, McClain C, Reinhart-King CA, King MR, Berk BC, Fujiwara K, Woo C-H, Abe J (2011a) PKCzeta mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation. J Cell Biol 193(5):867–884.  https://doi.org/10.1083/jcb.201010051 Google Scholar
  27. Heo KS, Fujiwara K, Abe J (2011b) Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. Circ J 75(12):2722–2730Google Scholar
  28. Heo KS, Chang E, Le NT, Cushman H, Yeh ET, Fujiwara K, Abe J (2013) De-SUMOylation enzyme of sentrin/SUMO-specific protease 2 regulates disturbed flow-induced SUMOylation of ERK5 and p53 that leads to endothelial dysfunction and atherosclerosis. Circ Res 112(6):911–923.  https://doi.org/10.1161/circresaha.111.300179 Google Scholar
  29. Heo KS, Fujiwara K, Abe J (2014) Shear stress and atherosclerosis. Mol Cells 37(6):435–440.  https://doi.org/10.14348/molcells.2014.0078 Google Scholar
  30. Heo KS, Le NT, Cushman HJ, Giancursio CJ, Chang E, Woo CH, Sullivan MA, Taunton J, Yeh ET, Fujiwara K, Abe J (2015) Disturbed flow-activated p90RSK kinase accelerates atherosclerosis by inhibiting SENP2 function. J Clin Investig 125(3):1299–1310.  https://doi.org/10.1172/jci76453 Google Scholar
  31. Heo KS, Berk BC, Abe J (2016) Disturbed flow-induced endothelial proatherogenic signaling via regulating post-translational modifications and epigenetic events. Antioxid Redox Signal 25(7):435–450.  https://doi.org/10.1089/ars.2015.6556 Google Scholar
  32. Heuslein JL, Gorick CM, Song J, Price RJ (2017) DNA methyltransferase 1-dependent dna hypermethylation constrains arteriogenesis by augmenting shear stress set point. J Am Heart Assoc 6(12):e007673.  https://doi.org/10.1161/jaha.117.007673 Google Scholar
  33. Hock MB, Kralli A (2009) Transcriptional control of mitochondrial biogenesis and function. Annu Rev Physiol 71:177–203.  https://doi.org/10.1146/annurev.physiol.010908.163119 Google Scholar
  34. Huang R, Hu Z, Cao Y, Li H, Zhang H, Su W, Xu Y, Liang L, Melgiri ND, Jiang L (2019) MiR-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting Cyclin D2 expression. EBioMedicine 40:685–694.  https://doi.org/10.1016/j.ebiom.2019.01.032 Google Scholar
  35. Illi B, Scopece A, Nanni S, Farsetti A, Morgante L, Biglioli P, Capogrossi MC, Gaetano C (2005) Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress. Circ Res 96(5):501–508.  https://doi.org/10.1161/01.res.0000159181.06379.63 Google Scholar
  36. Incalza MA, D’Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F (2018) Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vasc Pharmacol 100:1–19.  https://doi.org/10.1016/j.vph.2017.05.005 Google Scholar
  37. Jiang YZ, Jimenez JM, Ou K, McCormick ME, Zhang LD, Davies PF (2014) Hemodynamic disturbed flow induces differential DNA methylation of endothelial Kruppel-Like Factor 4 promoter in vitro and in vivo. Circ Res 115(1):32–43.  https://doi.org/10.1161/circresaha.115.303883 Google Scholar
  38. Kandi V, Vadakedath S (2015) Effect of DNA methylation in various diseases and the probable protective role of nutrition: a mini-review. Cureus 7(8):e309.  https://doi.org/10.7759/cureus.309 Google Scholar
  39. Kim M, Long TI, Arakawa K, Wang R, Yu MC, Laird PW (2010) DNA methylation as a biomarker for cardiovascular disease risk. PLoS ONE 5(3):e9692.  https://doi.org/10.1371/journal.pone.0009692 Google Scholar
  40. Kleinbongard P, Heusch G, Schulz R (2010) TNFalpha in atherosclerosis, myocardial ischemia/reperfusion and heart failure. Pharmacol Ther 127(3):295–314.  https://doi.org/10.1016/j.pharmthera.2010.05.002 Google Scholar
  41. Kotla S, Vu HT, Ko KA, Wang Y, Imanishi M, Heo KS, Fujii Y, Thomas TN, Gi YJ, Mazhar H, Paez-Mayorga J, Shin JH, Tao Y, Giancursio CJ, Medina JL, Taunton J, Lusis AJ, Cooke JP, Fujiwara K, Le NT, Abe JI (2019) Endothelial senescence is induced by phosphorylation and nuclear export of telomeric repeat binding factor 2-interacting protein. JCI Insight.  https://doi.org/10.1172/jci.insight.124867 Google Scholar
  42. Kulkarni NM, Muley MM, Jaji MS, Vijaykanth G, Raghul J, Reddy NK, Vishwakarma SL, Rajesh NB, Mookkan J, Krishnan UM, Narayanan S (2015) Topical atorvastatin ameliorates 12-O-tetradecanoylphorbol-13-acetate induced skin inflammation by reducing cutaneous cytokine levels and NF-kappaB activation. Arch Pharmacal Res 38(6):1238–1247.  https://doi.org/10.1007/s12272-014-0496-0 Google Scholar
  43. Kurzelewski M, Czarnowska E, Beresewicz A (2005) Superoxide- and nitric oxide-derived species mediate endothelial dysfunction, endothelial glycocalyx disruption, and enhanced neutrophil adhesion in the post-ischemic guinea-pig heart. J Physiol Pharmacol 56(2):163–178Google Scholar
  44. Lai B, Li Z, He M, Wang Y, Chen L, Zhang J, Yang Y, Shyy JY (2018) Atheroprone flow enhances the endothelial-to-mesenchymal transition. Am J Physiol Heart Circ Physiol 315(5):H1293–H1303.  https://doi.org/10.1152/ajpheart.00213.2018 Google Scholar
  45. Lee KK, Workman JL (2007) Histone acetyltransferase complexes: one size doesn’t fit all. Nat Rev Mol Cell Biol 8(4):284–295.  https://doi.org/10.1038/nrm2145 Google Scholar
  46. Lee JY, Park KS, Cho EJ, Joo HK, Lee SK, Lee SD, Park JB, Chang SJ, Jeon BH (2011) Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation. Biochem Biophys Res Commun 410(2):312–316.  https://doi.org/10.1016/j.bbrc.2011.05.139 Google Scholar
  47. Lee DY, Lee CI, Lin TE, Lim SH, Zhou J, Tseng YC, Chien S, Chiu JJ (2012) Role of histone deacetylases in transcription factor regulation and cell cycle modulation in endothelial cells in response to disturbed flow. Proc Natl Acad Sci USA 109(6):1967–1972.  https://doi.org/10.1073/pnas.1121214109 Google Scholar
  48. Lee DY, Lin TE, Lee CI, Zhou J, Huang YH, Lee PL, Shih YT, Chien S, Chiu JJ (2017) MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases. Proc Natl Acad Sci USA 114(8):2072–2077.  https://doi.org/10.1073/pnas.1621425114 Google Scholar
  49. Leisegang MS, Fork C, Josipovic I, Richter FM, Preussner J, Hu J, Miller MJ, Epah J, Hofmann P, Günther S, Moll F, Valasarajan C, Heidler J, Ponomareva Y, Freiman TM, Maegdefessel L, Plate KH, Mittelbronn M, Uchida S, Künne C, Stellos K, Schermuly RT, Weissmann N, Devraj K, Wittig I, Boon RA, Dimmeler S, Pullamsetti SS, Looso M, Miller FJ Jr, Brandes RP (2017) Long noncoding RNA MANTIS facilitates endothelial angiogenic function. Circulation 136(1):65–79.  https://doi.org/10.1161/circulationaha.116.026991 Google Scholar
  50. Li Z, Martin M, Zhang J, Huang HY, Bai L, Zhang J, Kang J, He M, Li J, Maurya MR, Gupta S, Zhou G, Sangwung P, Xu YJ, Huang HD, Jain M, Jain MK, Subramaniam S, Shyy JY (2017) Kruppel-like factor 4 regulation of cholesterol-25-hydroxylase and liver X receptor mitigates atherosclerosis susceptibility. Circulation 136(14):1315–1330.  https://doi.org/10.1161/circulationaha.117.027462 Google Scholar
  51. Libby P, Hansson GK (2015) Inflammation and immunity in diseases of the arterial tree: players and layers. Circ Res 116(2):307–311.  https://doi.org/10.1161/circresaha.116.301313 Google Scholar
  52. Liu WJ, Zhang XM, Wang N, Zhou XL, Fu YC, Luo LL (2015) Calorie restriction inhibits ovarian follicle development and follicle loss through activating SIRT1 signaling in mice. Eur J Med Res 20(1):22.  https://doi.org/10.1186/s40001-015-0114-8 Google Scholar
  53. Liu X, Tan H, Liu X, Wu Q (2018) Correlation between the expression of Drp1 in vascular endothelial cells and inflammatory factors in hypertension rats. Exp Ther Med 15(4):3892–3898.  https://doi.org/10.3892/etm.2018.5899 Google Scholar
  54. Martin D, Li Y, Yang J, Wang G, Margariti A, Jiang Z, Yu H, Zampetaki A, Hu Y, Xu Q, Zeng L (2014) Unspliced X-box-binding protein 1 (XBP1) protects endothelial cells from oxidative stress through interaction with histone deacetylase 3. J Biol Chem 289(44):30625–30634.  https://doi.org/10.1074/jbc.m114.571984 Google Scholar
  55. Martinon F (2010) Signaling by ROS drives inflammasome activation. Eur J Immunol 40(3):616–619.  https://doi.org/10.1002/eji.200940168 Google Scholar
  56. Matouk CC, Marsden PA (2008) Epigenetic regulation of vascular endothelial gene expression. Circ Res 102(8):873–887.  https://doi.org/10.1161/circresaha.107.171025 Google Scholar
  57. Montezano AC, De Lucca Camargo L, Persson P, Rios FJ, Harvey AP, Anagnostopoulou A, Palacios R, Gandara ACP, Alves-Lopes R, Neves KB, Dulak-Lis M, Holterman CE, de Oliveira PL, Graham D, Kennedy C, Touyz RM (2018) NADPH oxidase 5 is a pro-contractile Nox isoform and a point of cross-talk for calcium and redox signaling-implications in vascular function. J Am Heart Assoc.  https://doi.org/10.1161/jaha.118.009388 Google Scholar
  58. Munjal C, Givvimani S, Qipshidze N, Tyagi N, Falcone JC, Tyagi SC (2011) Mesenteric vascular remodeling in hyperhomocysteinemia. Mol Cell Biochem 348(1–2):99–108.  https://doi.org/10.1007/s11010-010-0643-y Google Scholar
  59. Neves KB, Rios FJ, van der Mey L, Alves-Lopes R, Cameron AC, Volpe M, Montezano AC, Savoia C, Touyz RM (2018) VEGFR (vascular endothelial growth factor receptor) inhibition induces cardiovascular damage via redox-sensitive processes. Hypertension 71(4):638–647.  https://doi.org/10.1161/hypertensionaha.117.10490 Google Scholar
  60. Niles JC, Wishnok JS, Tannenbaum SR (2006) Peroxynitrite-induced oxidation and nitration products of guanine and 8-oxoguanine: structures and mechanisms of product formation. Nitric Oxide 14(2):109–121.  https://doi.org/10.1016/j.niox.2005.11.001 Google Scholar
  61. Ogundele OM, Wasiu Gbolahan B, Emmanuel Cobham A, Azeez Olakunle I, Abdulbasit A (2017) Differential oxidative stress thresholds distinguishes cellular response to vascular occlusion and chemotoxicity in vivo. Drug Chem Toxicol 40(1):101–109.  https://doi.org/10.1080/01480545.2016.1188300 Google Scholar
  62. Paffen E, DeMaat MP (2006) C-reactive protein in atherosclerosis: a causal factor? Cardiovasc Res 71(1):30–39.  https://doi.org/10.1016/j.cardiores.2006.03.004 Google Scholar
  63. Panieri E, Santoro MM (2015) ROS signaling and redox biology in endothelial cells. Cell Mol Life Sci 72(17):3281–3303.  https://doi.org/10.1007/s00018-015-1928-9 Google Scholar
  64. Park SW, Noh HJ, Sung DJ, Kim JG, Kim JM, Ryu S-Y, Kang KJ, Kim B, Bae YM, Cho H (2015) Hydrogen peroxide induces vasorelaxation by enhancing 4-aminopyridine-sensitive Kv currents through S-glutathionylation. Pflugers Arch 467(2):285–297.  https://doi.org/10.1007/s00424-014-1513-3 Google Scholar
  65. Parmar KM, Larman HB, Dai G, Zhang Y, Wang ET, Moorthy SN, Kratz JR, Lin Z, Jain MK, Gimbrone MA Jr, García-Cardeña G (2006) Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J Clin Investig 116(1):49–58.  https://doi.org/10.1172/jci24787 Google Scholar
  66. Penna C, Tullio F, Femmino S, Rocca C, Angelone T, Cerra MC, Gallo MP, Gesmundo I, Fanciulli A, Brizzi MF, Pagliaro P, Alloatti G, Granata R (2017) Obestatin regulates cardiovascular function and promotes cardioprotection through the nitric oxide pathway. J Cell Mol Med 21(12):3670–3678.  https://doi.org/10.1111/jcmm.13277 Google Scholar
  67. Pi X, Xie L, Patterson C (2018) Emerging roles of vascular endothelium in metabolic homeostasis. Circ Res 123(4):477–494.  https://doi.org/10.1161/circresaha.118.313237 Google Scholar
  68. Potenza MA, Sgarra L, Nacci C, Leo V, De Salvia MA, Montagnani M (2019) Activation of AMPK/SIRT1 axis is required for adiponectin-mediated preconditioning on myocardial ischemia–reperfusion (I/R) injury in rats. PLoS ONE 14(1):e0210654.  https://doi.org/10.1371/journal.pone.0210654 Google Scholar
  69. Qiao C, Li S, Lu H, Meng F, Fan Y, Guo Y, Chen YE, Zhang J (2018) Laminar flow attenuates macrophage migration inhibitory factor expression in endothelial cells. Sci Rep.  https://doi.org/10.1038/s41598-018-20885-1 Google Scholar
  70. Rhoads K, Arderiu G, Charboneau A, Hansen SL, Hoffman W, Boudreau N (2005) A role for Hox A5 in regulating angiogenesis and vascular patterning. Lymphat Res Biol 3(4):240–252.  https://doi.org/10.1089/lrb.2005.3.240 Google Scholar
  71. Richardson B (2003) DNA methylation and autoimmune disease. Clin Immunol 109(1):72–79Google Scholar
  72. Robertson KD (2002) DNA methylation and chromatin—unraveling the tangled web. Oncogene 21(35):5361–5379.  https://doi.org/10.1038/sj.onc.1205609 Google Scholar
  73. Ross D, Zhou H, Siegel D (2011) Benzene toxicity: the role of the susceptibility factor NQO1 in bone marrow endothelial cell signaling and function. Chem Biol Interact 192(1–2):145–149.  https://doi.org/10.1016/j.cbi.2010.10.008 Google Scholar
  74. Roth SY, Denu JM, Allis CD (2001) Histone acetyltransferases. Annu Rev Biochem 70:81–120.  https://doi.org/10.1146/annurev.biochem.70.1.81 Google Scholar
  75. Salazar G (2018) NADPH oxidases and mitochondria in vascular senescence. Int J Mol Sci 19(5):1327.  https://doi.org/10.3390/ijms19051327 Google Scholar
  76. Sheehan AL, Carrell S, Johnson B, Stanic B, Banfi B, Miller FJ Jr (2011) Role for Nox1 NADPH oxidase in atherosclerosis. Atherosclerosis 216(2):321–326.  https://doi.org/10.1016/j.atherosclerosis.2011.02.028 Google Scholar
  77. Siedlecki P, Zielenkiewicz P (2006) Mammalian DNA methyltransferases. Acta Biochim Pol 53(2):245–256Google Scholar
  78. Smith BC, Denu JM (2009) Chemical mechanisms of histone lysine and arginine modifications. Biochim Biophys Acta 1789(1):45–57.  https://doi.org/10.1016/j.bbagrm.2008.06.005 Google Scholar
  79. Stancel N, Chen CC, Ke LY, Chu CS, Lu J, Sawamura T, Chen CH (2016) Interplay between CRP, atherogenic LDL, and LOX-1 and its potential role in the pathogenesis of atherosclerosis. Clin Chem 62(2):320–327.  https://doi.org/10.1373/clinchem.2015.243923 Google Scholar
  80. Su Y, Pelz C, Huang T, Torkenczy K, Wang X, Cherry A, Daniel CJ, Liang J, Nan X, Dai MS, Adey A, Impey S, Sears RC (2018) Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals. Genes Dev 32(21–22):1398–1419.  https://doi.org/10.1101/gad.314377.118 Google Scholar
  81. Suzuki T, Aizawa K, Matsumura T, Nagai R (2005) Vascular implications of the Kruppel-like family of transcription factors. Arterioscler Thromb Vasc Biol 25(6):1135–1141.  https://doi.org/10.1161/01.atv.0000165656.65359.23 Google Scholar
  82. Trento C, Marigo I, Pievani A, Galleu A, Dolcetti L, Wang C-Y, Serafini M, Bronte V, Dazzi F (2017) Bone marrow mesenchymal stromal cells induce nitric oxide synthase-dependent differentiation of CD11b(+) cells that expedite hematopoietic recovery. Haematologica 102(5):818–825.  https://doi.org/10.3324/haematol.2016.155390 Google Scholar
  83. Trojanowicz B, Ulrich C, Seibert E, Fiedler R, Girndt M (2014) Uremic conditions drive human monocytes to pro-atherogenic differentiation via an angiotensin-dependent mechanism. PLoS ONE 9(7):e102137.  https://doi.org/10.1371/journal.pone.0102137 Google Scholar
  84. Vara D, Watt JM, Fortunato TM, Mellor H, Burgess M, Wicks K, Mace K, Reeksting S, Lubben A, Wheeler-Jones CPD, Pula G (2018) Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis. Antioxid Redox Signal 28(2):110–130.  https://doi.org/10.1089/ars.2016.6869 Google Scholar
  85. Wang H, Hartnett ME (2017) Roles of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in angiogenesis: isoform-specific effects. Antioxidants (Basel) 6(2):40.  https://doi.org/10.3390/antiox6020040 Google Scholar
  86. Wang W, Ha CH, Jhun BS, Wong C, Jain MK, Jin ZG (2010) Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5 and mediates expression of KLF2 and eNOS. Blood 115(14):2971–2979.  https://doi.org/10.1182/blood-2009-05-224824 Google Scholar
  87. Wang WR, Liu EQ, Zhang JY, Li YX, Yang XF, He YH, Zhang W, Jing T, Lin R (2015) Activation of PPAR alpha by fenofibrate inhibits apoptosis in vascular adventitial fibroblasts partly through SIRT1-mediated deacetylation of FoxO1. Exp Cell Res 338(1):54–63.  https://doi.org/10.1016/j.yexcr.2015.07.027 Google Scholar
  88. Wang H, Zhou Y, Guo Z, Dong Y, Xu J, Huang H, Liu H, Wang W (2018) Sitagliptin attenuates endothelial dysfunction of Zucker diabetic fatty rats: implication of the antiperoxynitrite and autophagy. J Cardiovasc Pharmacol Ther 23(1):66–78.  https://doi.org/10.1177/1074248417715001 Google Scholar
  89. Weber M, Baker MB, Moore JP, Searles CD (2010) MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity. Biochem Biophys Res Commun 393(4):643–648.  https://doi.org/10.1016/j.bbrc.2010.02.045 Google Scholar
  90. Witty J, Aguilar-Martinez E, Sharrocks AD (2010) SENP1 participates in the dynamic regulation of Elk-1 SUMOylation. Biochem J 428(2):247–254.  https://doi.org/10.1042/bj20091948 Google Scholar
  91. Wong BW, Meredith A, Lin D, McManus BM (2012) The biological role of inflammation in atherosclerosis. Can J Cardiol 28(6):631–641.  https://doi.org/10.1016/j.cjca.2012.06.023 Google Scholar
  92. Woo CH, Shishido T, McClain C, Lim JH, Li JD, Yang J, Yan C, Abe J (2008) Extracellular signal-regulated kinase 5 SUMOylation antagonizes shear stress-induced antiinflammatory response and endothelial nitric oxide synthase expression in endothelial cells. Circ Res 102(5):538–545.  https://doi.org/10.1161/circresaha.107.156877 Google Scholar
  93. Yang T, Peleli M, Zollbrecht C, Giulietti A, Terrando N, Lundberg JO, Weitzberg E, Carlström M (2015) Inorganic nitrite attenuates NADPH oxidase-derived superoxide generation in activated macrophages via a nitric oxide-dependent mechanism. Free Radic Biol Med 83:159–166.  https://doi.org/10.1016/j.freeradbiomed.2015.02.016 Google Scholar
  94. Yang Q, Xu J, Ma Q, Liu Z, Sudhakar V, Cao Y, Wang L, Zeng X, Zhou Y, Zhang M, Xu Y, Wang Y, Weintraub NL, Zhang C, Fukai T, Wu C, Huang L, Han Z, Wang T, Fulton DJ, Hong M, Huo Y (2018a) PRKAA1/AMPKalpha1-driven glycolysis in endothelial cells exposed to disturbed flow protects against atherosclerosis. Nat Commun 9(1):4667.  https://doi.org/10.1038/s41467-018-07132-x Google Scholar
  95. Yang H, Bai W, Gao L, Jiang J, Tang Y, Niu Y, Lin H, Li L (2018b) Mangiferin alleviates hypertension induced by hyperuricemia via increasing nitric oxide releases. J Pharmacol Sci 137(2):154–161.  https://doi.org/10.1016/j.jphs.2018.05.008 Google Scholar
  96. Yeh ET (2009) SUMOylation and De-SUMOylation: wrestling with life’s processes. J Biol Chem 284(13):8223–8227.  https://doi.org/10.1074/jbc.r800050200 Google Scholar
  97. Zeng L, Zhang Y, Chien S, Liu X, Shyy JY (2003) The role of p53 deacetylation in p21Waf1 regulation by laminar flow. J Biol Chem 278(27):24594–24599.  https://doi.org/10.1074/jbc.m301955200 Google Scholar
  98. Zhao Y, Vanhoutte PM, Leung SW (2015) Vascular nitric oxide: beyond eNOS. J Pharmacol Sci 129(2):83–94.  https://doi.org/10.1016/j.jphs.2015.09.002 Google Scholar
  99. Zhou J, Wang KC, Wu W, Subramaniam S, Shyy JY, Chiu JJ, Li JY, Chien S (2011) MicroRNA-21 targets peroxisome proliferators-activated receptor-alpha in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proc Natl Acad Sci USA 108(25):10355–10360.  https://doi.org/10.1073/pnas.1107052108 Google Scholar
  100. Zhou J, Li YS, Wang KC, Chien S (2014) Epigenetic mechanism in regulation of endothelial function by disturbed flow: induction of DNA hypermethylation by DNMT1. Cell Mol Bioeng 7(2):218–224.  https://doi.org/10.1007/s12195-014-0325-z Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.Department of PharmacologyChungnam National University College of PharmacyDaejeonRepublic of Korea
  2. 2.Institute of Drug Research & DevelopmentChungnam National UniversityDaejeonRepublic of Korea

Personalised recommendations