REFERENCES
2. Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006;6:508-19.
3. Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res. 2014;114:1852-66.
4. Martin SS, Aday AW, Allen NB, et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Committee. 2025 heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation. 2025;151:e41-e660.
5. Gaba P, Gersh BJ, Muller J, Narula J, Stone GW. Evolving concepts of the vulnerable atherosclerotic plaque and the vulnerable patient: implications for patient care and future research. Nat Rev Cardiol. 2023;20:181-96.
6. Xu S, Ilyas I, Little PJ, et al. Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: from mechanism to pharmacotherapies. Pharmacol Rev. 2021;73:924-67.
7. Welt FGP, Batchelor W, Spears JR, et al. Reperfusion injury in patients with acute myocardial infarction: JACC scientific statement. J Am Coll Cardiol. 2024;83:2196-213.
8. Konijnenberg LSF, Damman P, Duncker DJ, et al. Pathophysiology and diagnosis of coronary microvascular dysfunction in ST-elevation myocardial infarction. Cardiovasc Res. 2020;116:787-805.
9. Ross R, Glomset JA. The pathogenesis of atherosclerosis (first of two parts). N Engl J Med. 1976;295:369-77.
12. Anderson TJ, Gerhard MD, Meredith IT, et al. Systemic nature of endothelial dysfunction in atherosclerosis. Am J Cardiol. 1995;75:71B-4B.
13. Furchgott RF. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. Jama. ;1996:276:1186-8.
14. Glagov S, Zarins C, Giddens DP, et al. Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med. 1988;112:1018-31.
15. Mussbacher M, Schossleitner K, Kral-Pointner JB, Salzmann M, Schrammel A, Schmid JA. More than just a monolayer: the multifaceted role of endothelial cells in the pathophysiology of atherosclerosis. Curr Atheroscler Rep. 2022;24:483-92.
16. Gimbrone MA Jr, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res. 2016;118:620-36.
17. Cimmino G, Muscoli S, De Rosa S, et al; Pathogenesis Of Atherosclerosis Working Group Of The Italian Society Of Cardiology. Evolving concepts in the pathophysiology of atherosclerosis: from endothelial dysfunction to thrombus formation through multiple shades of inflammation. J Cardiovasc Med. 2023;24:e156-67.
18. Ludmer PL, Selwyn AP, Shook TL, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046-51.
19. Bossaller C, Habib GB, Yamamoto H, Williams C, Wells S, Henry PD. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5’-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest. 1987;79:170-4.
20. d’Uscio LV, Smith LA, Katusic ZS. Hypercholesterolemia impairs endothelium-dependent relaxations in common carotid arteries of apolipoprotein e-deficient mice. Stroke. 2001;32:2658-64.
21. Ghanta SN, Kattamuri LPV, Odueke A, Mehta JL. Molecular insights into ischemia-reperfusion injury in coronary artery disease: mechanisms and therapeutic implications: a comprehensive review. Antioxidants. 2025;14:213.
22. de Winther MPJ, Bäck M, Evans P, et al. Translational opportunities of single-cell biology in atherosclerosis. Eur Heart J. 2023;44:1216-30.
23. Chen Y, Yuan C, Qin W, et al. TMAO promotes vascular endothelial cell pyroptosis via the LPEAT-mitophagy pathway. Biochem Biophys Res Commun. 2024;703:149667.
24. Wehbe Z, Wehbe M, Al Khatib A, et al. Emerging understandings of the role of exosomes in atherosclerosis. J Cell Physiol. 2025;240:e31454.
25. Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol. 2014;34:509-15.
26. Mente A, de Koning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med. 2009;169:659-69.
27. Renaud S, Lanzmann-Petithory D. Coronary heart disease: dietary links and pathogenesis. Public Health Nutr. 2001;4:459-74.
28. Shao C, Wang J, Tian J, Tang Y. Coronary artery disease: from mechanism to clinical practice. In: Wang M, editor. Coronary Artery Disease: Therapeutics and drug discovery. Singapore: Springer; 2020. pp. 1-36.
30. De Bosscher R, Dausin C, Claus P, et al. Lifelong endurance exercise and its relation with coronary atherosclerosis. Eur Heart J. 2023;44:2388-99.
31. Nishitani-Yokoyama M, Miyauchi K, Shimada K, et al. Impact of physical activity on coronary plaque volume and components in acute coronary syndrome patients after early phase ii cardiac rehabilitation. Circ J. 2018;83:101-9.
32. Tibuakuu M, Michos ED, Navas-Acien A, Jones MR. Air pollution and cardiovascular disease: a focus on vulnerable populations worldwide. Curr Epidemiol Rep. 2018;5:370-8.
33. Hinterdobler J, Schott S, Jin H, et al. Acute mental stress drives vascular inflammation and promotes plaque destabilization in mouse atherosclerosis. Eur Heart J. 2021;42:4077-88.
34. Wirtz PH, von Känel R. Psychological stress, inflammation, and coronary heart disease. Curr Cardiol Rep. 2017;19:111.
35. Chen X, Liu M, Zuo L, et al. Environmental noise exposure and health outcomes: an umbrella review of systematic reviews and meta-analysis. Eur J Public Health. 2023;33:725-31.
36. Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol. 2019;234:16812-23.
37. Poredos P, Poredos AV, Gregoric I. Endothelial dysfunction and its clinical implications. Angiology. 2021;72:604-15.
38. Stancu CS, Toma L, Sima AV. Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis. Cell Tissue Res. 2012;349:433-46.
39. Gofman JW, Lindgren F. The role of lipids and lipoproteins in atherosclerosis. Science. 1950;111:166-71.
40. Rhee M, Lee J, Lee EY, Yoon KH, Lee SH. Lipid variability induces endothelial dysfunction by increasing inflammation and oxidative stress. Endocrinol Metab. 2024;39:511-20.
41. Incalza MA, D’Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol. 2018;100:1-19.
42. Terasaka N, Yu S, Yvan-Charvet L, et al. ABCG1 and HDL protect against endothelial dysfunction in mice fed a high-cholesterol diet. J Clin Invest. 2008;118:3701-13.
43. Besler C, Heinrich K, Rohrer L, et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest. 2011;121:2693-708.
44. Nicholls SJ, Zheng L, Hazen SL. Formation of dysfunctional high-density lipoprotein by myeloperoxidase. Trends Cardiovasc Med. 2005;15:212-9.
45. Eren E, Yilmaz N, Aydin O. Functionally defective high-density lipoprotein and paraoxonase: a couple for endothelial dysfunction in atherosclerosis. Cholesterol. 2013;2013:792090.
46. Zhang C, Zhou T, Chen Z, et al. Coupling of integrin α5 to annexin A2 by flow drives endothelial activation. Circ Res. 2020;127:1074-90.
47. Zhou M, Yu Y, Chen R, et al. Wall shear stress and its role in atherosclerosis. Front Cardiovasc Med. 2023;10:1083547.
48. Nigro P, Abe J, Berk BC. Flow shear stress and atherosclerosis: a matter of site specificity. Antioxid Redox Signal. 2011;15:1405-14.
49. Wang X, Shen Y, Shang M, Liu X, Munn LL. Endothelial mechanobiology in atherosclerosis. Cardiovasc Res. 2023;119:1656-75.
50. Baeyens N, Bandyopadhyay C, Coon BG, Yun S, Schwartz MA. Endothelial fluid shear stress sensing in vascular health and disease. J Clin Invest. 2016;126:821-8.
51. Conway DE, Breckenridge MT, Hinde E, Gratton E, Chen CS, Schwartz MA. Fluid shear stress on endothelial cells modulates mechanical tension across VE-cadherin and PECAM-1. Curr Biol. 2013;23:1024-30.
52. Tzima E, Irani-Tehrani M, Kiosses WB, et al. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature. 2005;437:426-31.
53. Fleming I, Fisslthaler B, Dixit M, Busse R. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells. J Cell Sci. 2005;118:4103-11.
54. He S, Huang L, Chen Z, Yuan Z, Zhao Y, Zeng L, Zhu Y, He J. Disruption of the novel nested gene aff3ir mediates disturbed flow-induced atherosclerosis in mice. eLife. 2025;13:RP103413.
55. Wang F, Wang SY, Gu Y, et al. Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation. Clin Transl Med. 2025;15:e70168.
56. Lv Y, Jiang Z, Zhou W, et al. Low-shear stress promotes atherosclerosis via inducing endothelial cell pyroptosis mediated by IKKε/STAT1/NLRP3 Pathway. Inflammation. 2024;47:1053-66.
57. Nakayama A, Albarrán-Juárez J, Liang G, et al. Disturbed flow-induced Gs-mediated signaling protects against endothelial inflammation and atherosclerosis. JCI Insight. 2020;5:140485.
58. Wang Y, Qiu J, Luo S, et al. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis. Regen Biomater. 2016;3:257-67.
59. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987;84:9265-9.
60. Ignarro LJ, Buga GM, Wei LH, Bauer PM, Wu G, del Soldato P. Role of the arginine-nitric oxide pathway in the regulation of vascular smooth muscle cell proliferation. Proc Natl Acad Sci U S A. 2001;98:4202-8.
61. Hutchinson PJ, Palmer RM, Moncada S. Comparative pharmacology of EDRF and nitric oxide on vascular strips. Eur J Pharmacol. 1987;141:445-51.
62. Radomski MW, Palmer RM, Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol. 1987;92:181-7.
63. Griffith TM, Edwards DH, Lewis MJ, Newby AC, Henderson AH. The nature of endothelium-derived vascular relaxant factor. Nature. 1984;308:645-7.
64. Rapoport RM, Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res. 1983;52:352-7.
65. Sessa WC, Harrison JK, Barber CM, et al. Molecular cloning and expression of a cDNA encoding endothelial cell nitric oxide synthase. J Biol Chem. 1992;267:15274-6.
67. Dudzinski DM, Michel T. Life history of eNOS: partners and pathways. Cardiovasc Res. 2007;75:247-60.
68. Bucci M, Gratton JP, Rudic RD, et al. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat Med. 2000;6:1362-7.
69. Sandoo A, van Zanten JJ, Metsios GS, Carroll D, Kitas GD. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J. 2010;4:302-12.
70. Kuchan MJ, Frangos JA. Role of calcium and calmodulin in flow-induced nitric oxide production in endothelial cells. Am J Physiol. 1994;266:C628-36.
71. Gimbrone MA Jr, García-Cardeña G. Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis. Cardiovasc Pathol. 2013;22:9-15.
72. Chiu JJ, Chien S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev. 2011;91:327-87.
73. Lee MR, Li L, Kitazawa T. Cyclic GMP causes Ca2+ desensitization in vascular smooth muscle by activating the myosin light chain phosphatase. J Biol Chem. 1997;272:5063-8.
74. Gao Y, Chen Z, Leung SW, Vanhoutte PM. Hypoxic vasospasm mediated by cIMP: when soluble guanylyl cyclase turns bad. J Cardiovasc Pharmacol. 2015;65:545-8.
75. Kraehling JR, Sessa WC. Contemporary Approaches to Modulating the Nitric Oxide-cGMP Pathway in Cardiovascular Disease. Circ Res. 2017;120:1174-82.
76. Procter NE, Chong CR, Sverdlov AL, Chan WP, Chirkov YY, Horowitz JD. Aging of platelet nitric oxide signaling: pathogenesis, clinical implications, and therapeutics. Semin Thromb Hemost. 2014;40:660-8.
77. Radomski MW, Palmer RM, Moncada S. Modulation of platelet aggregation by an L-arginine-nitric oxide pathway. Trends Pharmacol Sci. 1991;12:87-8.
78. Bath PM. The effect of nitric oxide-donating vasodilators on monocyte chemotaxis and intracellular cGMP concentrations in vitro. Eur J Clin Pharmacol. 1993;45:53-8.
79. Kuhlencordt PJ, Rosel E, Gerszten RE, et al. Role of endothelial nitric oxide synthase in endothelial activation: insights from eNOS knockout endothelial cells. Am J Physiol Cell Physiol. 2004;286:C1195-202.
80. Huang PL. Lessons learned from nitric oxide synthase knockout animals. Semin Perinatol. 2000;24:87-90.
81. Kuhlencordt PJ, Gyurko R, Han F, et al. Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice. Circulation. 2001;104:448-54.
82. Freiman PC, Mitchell GG, Heistad DD, Armstrong ML, Harrison DG. Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates. Circ Res. 1986;58:783-9.
83. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109:III27-32.
84. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33:829-37.
85. Garcia V, Sessa WC. Endothelial NOS: perspective and recent developments. Br J Pharmacol. 2019;176:189-96.
86. Aulak KS, Barnes JW, Tian L, et al. Specific O-GlcNAc modification at Ser-615 modulates eNOS function. Redox Biol. 2020;36:101625.
87. Qin JZ, Wang SJ, Xia C. microRNAs regulate nitric oxide release from endothelial cells by targeting NOS3. J Thromb Thrombolysis. 2018;46:275-82.
88. Bonauer A, Carmona G, Iwasaki M, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009;324:1710-3.
89. Chistiakov DA, Sobenin IA, Orekhov AN, Bobryshev YV. Human miR-221/222 in physiological and atherosclerotic vascular remodeling. Biomed Res Int. 2015;2015:354517.
90. Chen PY, Qin L, Baeyens N, et al. Endothelial-to-mesenchymal transition drives atherosclerosis progression. J Clin Invest. 2015;125:4514-28.
91. Evrard SM, Lecce L, Michelis KC, et al. Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability. Nat Commun. 2016;7:11853.
92. Zhao G, Lu H, Liu Y, et al. Single-cell transcriptomics reveals endothelial plasticity during diabetic atherogenesis. Front Cell Dev Biol. 2021;9:689469.
93. Huang Q, Gan Y, Yu Z, Wu H, Zhong Z. Endothelial to mesenchymal transition: an insight in atherosclerosis. Front Cardiovasc Med. 2021;8:734550.
94. Chen PY, Qin L, Li G, et al. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nat Metab. 2019;1:912-26.
95. Zhang Z, Guo Q, Ma C, et al. USF1 transcriptionally activates USP14 to drive atherosclerosis by promoting EndMT through NLRC5/Smad2/3 axis. Mol Med. 2024;30:32.
96. Chen LJ, Li JY, Nguyen P, et al. Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow. Proc Natl Acad Sci U S A. 2024;121:e2318904121.
97. Singh A, Bhatt KS, Nguyen HC, Frisbee JC, Singh KK. Endothelial-to-mesenchymal transition in cardiovascular pathophysiology. Int J Mol Sci. 2024;25:6180.
98. Dong M, Zhang Y, Chen M, et al. ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT. Acta Pharm Sin B. 2024;14:3027-48.
99. Lecce L, Xu Y, V’Gangula B, et al. Histone deacetylase 9 promotes endothelial-mesenchymal transition and an unfavorable atherosclerotic plaque phenotype. J Clin Invest. 2021:131.
100. Murugavel S, Bugyei-Twum A, Matkar PN, et al. Valproic acid induces endothelial-to-mesenchymal transition-like phenotypic switching. Front Pharmacol. 2018;9:737.
101. Zhao J, Zhao C, Yang F, et al. DNMT1 mediates the disturbed flow-induced endothelial to mesenchymal transition through disrupting β-alanine and carnosine homeostasis. Theranostics. 2023;13:4392-411.
102. Wakabayashi T, Naito H. Cellular heterogeneity and stem cells of vascular endothelial cells in blood vessel formation and homeostasis: Insights from single-cell RNA sequencing. Front Cell Dev Biol. 2023;11:1146399.
103. Kalucka J, de Rooij LPMH, Goveia J, et al. Single-cell transcriptome atlas of murine endothelial cells. Cell. 2020;180:764-779.e20.
104. Kalluri AS, Vellarikkal SK, Edelman ER, et al. Single-Cell analysis of the normal mouse aorta reveals functionally distinct endothelial cell populations. Circulation. 2019;140:147-63.
105. He D, Mao A, Zheng CB, et al. Aortic heterogeneity across segments and under high fat/salt/glucose conditions at the single-cell level. Natl Sci Rev. 2020;7:881-96.
106. Tan J, Liang Y, Yang Z, et al. Single-cell transcriptomics reveals crucial cell subsets and functional heterogeneity associated with carotid atherosclerosis and cerebrovascular events. Arterioscler Thromb Vasc Biol. 2023;43:2312-32.
107. Jakubowski H, Witucki Ł. Homocysteine metabolites, endothelial dysfunction, and cardiovascular disease. Int J Mol Sci. 2025;26:746.
108. Jakubowski H. Homocysteine modification in protein structure/function and human disease. Physiol Rev. 2019;99:555-604.
109. Gurda D, Handschuh L, Kotkowiak W, Jakubowski H. Homocysteine thiolactone and N-homocysteinylated protein induce pro-atherogenic changes in gene expression in human vascular endothelial cells. Amino Acids. 2015;47:1319-39.
110. Witucki Ł, Jakubowski H. Homocysteine metabolites impair the PHF8/H4K20me1/mTOR/autophagy pathway by upregulating the expression of histone demethylase PHF8-targeting microRNAs in human vascular endothelial cells and mice. FASEB J. 2024;38:e70072.
111. Jakubowski H, Zhang L, Bardeguez A, Aviv A. Homocysteine thiolactone and protein homocysteinylation in human endothelial cells: implications for atherosclerosis. Circ Res. 2000;87:45-51.
112. Xiang P, Chen Q, Chen L, et al. Metabolite Neu5Ac triggers SLC3A2 degradation promoting vascular endothelial ferroptosis and aggravates atherosclerosis progression in ApoE-/- mice. Theranostics. 2023;13:4993-5016.
113. Boutagy NE, Gamez-Mendez A, Fowler JW, et al. Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice. J Clin Invest. 2024:134.
114. Brown JM, Hazen SL. Microbial modulation of cardiovascular disease. Nat Rev Microbiol. 2018;16:171-81.
115. Qian B, Zhang K, Li Y, Sun K. Update on gut microbiota in cardiovascular diseases. Front Cell Infect Microbiol. 2022;12:1059349.
116. Luqman A, Hassan A, Ullah M, et al. Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder. Front Immunol. 2024;15:1321395.
117. Querio G, Antoniotti S, Geddo F, Levi R, Gallo MP. Modulation of endothelial function by TMAO, a gut microbiota-derived metabolite. Int J Mol Sci. 2023;24:5806.
118. Querio G, Antoniotti S, Geddo F, Levi R, Gallo MP. Trimethylamine N-oxide (TMAO) impairs purinergic induced intracellular calcium increase and nitric oxide release in endothelial Cells. Int J Mol Sci. 2022;23:3982.
119. Ma G, Pan B, Chen Y, et al. Trimethylamine N-oxide in atherogenesis: impairing endothelial self-repair capacity and enhancing monocyte adhesion. Biosci Rep. 2017;37:BSR20160244.
120. Singh GB, Zhang Y, Boini KM, Koka S. High mobility group box 1 mediates TMAO-induced endothelial dysfunction. Int J Mol Sci. 2019;20:3570.
121. Bingyu W, Jun Q, Bingyang L, Xi Y, Jianqing Z, Jiangfang L. Trimethylamine N-oxide promotes PERK-mediated endothelial-mesenchymal transition and apoptosis thereby aggravates atherosclerosis. Int Immunopharmacol. 2024;142:113209.
122. Seldin MM, Meng Y, Qi H, et al. Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-κB. J Am Heart Assoc. 2016;5:e002767.
123. Yu B, Yuan C, Chen J, et al. TMAO induces pyroptosis of vascular endothelial cells and atherosclerosis in ApoE-/- mice via MBOAT2-mediated endoplasmic reticulum stress. Biochim Biophys Acta Mol Cell Biol Lipids. 2024;1869:159559.
124. Wu P, Chen J, Chen J, et al. Trimethylamine N-oxide promotes ApoE-/- mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway. J Cell Physiol. 2020;235:6582-91.
125. Zhu Y, Yin C, Wang Y. Probiotic enterococcus faecium attenuated atherosclerosis by improving SCFAs associated with gut microbiota in ApoE-/- mice. Bioengineering. 2024;11:1033.
126. Yang H, Yang Y, Cui G, et al. Dietary methionine restriction ameliorates atherosclerosis by remodeling the gut microbiota in apolipoprotein E-knockout mice. Food Funct. 2025;16:4904-22.
127. Luo Z, Yang L, Zhu T, et al. Aucubin ameliorates atherosclerosis by modulating tryptophan metabolism and inhibiting endothelial-mesenchymal transitions via gut microbiota regulation. Phytomedicine. 2024;135:156122.
128. Nageswaran V, Carreras A, Reinshagen L, et al. Gut microbial metabolite imidazole propionate impairs endothelial cell function and promotes the development of atherosclerosis. Arterioscler Thromb Vasc Biol. 2025;45:823-39.
129. Paone S, Baxter AA, Hulett MD, Poon IKH. Endothelial cell apoptosis and the role of endothelial cell-derived extracellular vesicles in the progression of atherosclerosis. Cell Mol Life Sci. 2019;76:1093-106.
130. Lin W, Huang F, Yuan Y, et al. Endothelial exosomes work as a functional mediator to activate macrophages. Front Immunol. 2023;14:1169471.
131. He S, Wu C, Xiao J, Li D, Sun Z, Li M. Endothelial extracellular vesicles modulate the macrophage phenotype: Potential implications in atherosclerosis. Scand J Immunol. 2018;87:e12648.
132. Chang YJ, Li YS, Wu CC, et al. Extracellular MicroRNA-92a mediates endothelial cell-macrophage communication. Arterioscler Thromb Vasc Biol. 2019;39:2492-504.
133. Bennett MR, Sinha S, Owens GK. Vascular smooth muscle cells in atherosclerosis. Circ Res. 2016;118:692-702.
134. Wang H, Xie Y, Salvador AM, et al. Exosomes: multifaceted messengers in atherosclerosis. Curr Atheroscler Rep. 2020;22:57.
135. Zhang Z, Yi D, Zhou J, et al. Exosomal LINC01005 derived from oxidized low-density lipoprotein-treated endothelial cells regulates vascular smooth muscle cell phenotypic switch. Biofactors. 2020;46:743-53.
136. Dabravolski SA, Sukhorukov VN, Glanz VY, Pleshko EM, Orekhov NA, Sobenin IA. Exosomes in atherosclerosis: role in the pathogenesis and targets for therapy. Curr Med Chem. 2025;32:3106-21.
137. Xu L, Geng T, Zang G, et al. Exosome derived from CD137-modified endothelial cells regulates the Th17 responses in atherosclerosis. J Cell Mol Med. 2020;24:4659-67.
138. Gao H, Wang X, Lin C, et al. Exosomal MALAT1 derived from ox-LDL-treated endothelial cells induce neutrophil extracellular traps to aggravate atherosclerosis. Biol Chem. 2020;401:367-76.
139. Chen L, Hu L, Li Q, Ma J, Li H. Exosome-encapsulated miR-505 from ox-LDL-treated vascular endothelial cells aggravates atherosclerosis by inducing NET formation. Acta Biochim Biophys Sin. 2019;51:1233-41.
140. Liu P, Wang S, Wang G, et al. Macrophage-derived exosomal miR-4532 promotes endothelial cells injury by targeting SP1 and NF-κB P65 signalling activation. J Cell Mol Med. 2022;26:5165-80.
141. Tang N, Sun B, Gupta A, Rempel H, Pulliam L. Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-κB in endothelial cells. FASEB J. 2016;30:3097-106.
142. Chen S, Zhou H, Zhang B, Hu Q. Exosomal miR-512-3p derived from mesenchymal stem cells inhibits oxidized low-density lipoprotein-induced vascular endothelial cells dysfunction via regulating Keap1. J Biochem Mol Toxicol. 2021;35:1-11.
143. Xing X, Li Z, Yang X, et al. Adipose-derived mesenchymal stem cells-derived exosome-mediated microRNA-342-5p protects endothelial cells against atherosclerosis. Aging. 2020;12:3880-98.
144. Li J, Tan M, Xiang Q, Zhou Z, Yan H. Thrombin-activated platelet-derived exosomes regulate endothelial cell expression of ICAM-1 via microRNA-223 during the thrombosis-inflammation response. Thromb Res. 2017;154:96-105.
145. Segal SS, Bagher P. Regulation of myoendothelial junction formation: bridging the gap. Circ Res. 2010;106:1014-6.
146. Shu X, Ruddiman CA, Keller TCS 4th, et al. Heterocellular contact can dictate arterial function. Circ Res. 2019;124:1473-81.
147. Lemmey HA, Garland CJ, Dora KA. Intrinsic regulation of microvascular tone by myoendothelial feedback circuits. Curr Top Membr. 2020;85:327-55.
148. Straub AC, Zeigler AC, Isakson BE. The myoendothelial junction: connections that deliver the message. Physiology. 2014;29:242-9.
149. Ledoux J, Taylor MS, Bonev AD, et al. Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted spaces of myoendothelial projections. Proc Natl Acad Sci U S A. 2008;105:9627-32.
150. Han Y, Huang K, Yao Q, Jiang Z. Mechanobiology in vascular remodeling. Nat Sci Rev. 2018;5:933-46.
151. Lateef OM, Foote CA, Ramirez-perez FI, et al. Vascular smooth muscle cell mechanical stretch modulates tissue transglutaminase activity and cytoskeletal dynamics. Physiology. 2024;39:735.
152. Zaric B, Obradovic M, Trpkovic A, Banach M, Mikhailidis DP, Isenovic ER. Endothelial dysfunction in dyslipidaemia: molecular mechanisms and clinical implications. Curr Med Chem. 2020;27:1021-40.
153. Gao D, Hua R, Jiesisibieke D, et al. C-reactive protein and coronary atheroma regression following statin therapy: a meta-regression of randomized controlled trials. Front Cardiovasc Med. 2022;9:989527.
154. Egede R, Jensen LO, Hansen HS, et al. Effect of intensive lipid-lowering treatment compared to moderate lipid-lowering treatment with rosuvastatin on endothelial function in high risk patients. Int J Cardiol. 2012;158:376-9.
155. Takayama T, Hiro T, Yoda S, et al. Effect of aggressive lipid-lowering treatment with rosuvastatin on vascular endoTHelium function: evaluation of vascular endothelium function (EARTH study). Heart Vessels. 2018;33:590-4.
156. Kater AL, Batista MC, Ferreira SR. Improved endothelial function with simvastatin but unchanged insulin sensitivity with simvastatin or ezetimibe. Metabolism. 2010;59:921-6.
157. Ziogos E, Chelko SP, Harb T, et al. Platelet activation and endothelial dysfunction biomarkers in acute coronary syndrome: the impact of PCSK9 inhibition. Eur Heart J Cardiovasc Pharmacother. 2023;9:636-46.
158. Liu S, Wu J, Stolarz A, et al. PCSK9 attenuates efferocytosis in endothelial cells and promotes vascular aging. Theranostics. 2023;13:2914-29.
159. Taddei S, Virdis A, Ghiadoni L, Sudano I, Salvetti A. Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. Drugs. 2002;62:265-84.
160. Miyamoto M, Kotani K, Ishibashi S, Taniguchi N. The effect of antihypertensive drugs on endothelial function as assessed by flow-mediated vasodilation in hypertensive patients. Int J Vasc Med. 2012;2012:453264.
161. Flammer AJ, Gössl M, Li J, et al. Renin inhibition with aliskiren lowers circulating endothelial progenitor cells in patients with early atherosclerosis. J Hypertens. 2013;31:632-5.
162. Virdis A, Ghiadoni L, Taddei S. Effects of antihypertensive treatment on endothelial function. Curr Hypertens Rep. 2011;13:276-81.
163. Wang Y, Yao M, Wang J, et al. Effects of antidiabetic drugs on endothelial function in patients with type 2 diabetes mellitus: a bayesian network meta-analysis. Front Endocrinol. 2022;13:818537.
164. Maruhashi T, Higashi Y. Pathophysiological association between diabetes mellitus and endothelial dysfunction. Antioxidants. 2021;10:1306.
165. Dandona P, Aljada A. Endothelial dysfunction in patients with type 2 diabetes and the effects of thiazolidinedione antidiabetic agents. J Diabetes Complications. 2004;18:91-102.
166. Pereira CA, Carneiro FS, Matsumoto T, Tostes RC. Bonus effects of antidiabetic drugs: possible beneficial effects on endothelial dysfunction, vascular inflammation and atherosclerosis. Basic Clin Pharmacol Toxicol. 2018;123:523-38.
167. Huang AL, Vita JA. Effects of systemic inflammation on endothelium-dependent vasodilation. Trends Cardiovasc Med. 2006;16:15-20.
168. Shao Y, Cheng Z, Li X, Chernaya V, Wang H, Yang XF. Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction-a novel mechanism for maintaining vascular function. J Hematol Oncol. 2014;7:80.
169. Vera M, Torramade-Moix S, Martin-Rodriguez S, et al. Antioxidant and anti-inflammatory strategies based on the potentiation of glutathione peroxidase activity prevent endothelial dysfunction in chronic kidney disease. Cell Physiol Biochem. 2018;51:1287-300.
170. Penna C, Pagliaro P. Endothelial dysfunction: redox imbalance, NLRP3 inflammasome, and inflammatory responses in cardiovascular diseases. Antioxidants. 2025;14:256.
171. van der Heijden T, Kritikou E, Venema W, et al. NLRP3 Inflammasome inhibition by MCC950 reduces atherosclerotic lesion development in apolipoprotein E-deficient mice-brief report. Arterioscler Thromb Vasc Biol. 2017;37:1457-61.
172. Kajikawa M, Higashi Y, Tomiyama H, et al. Effect of short-term colchicine treatment on endothelial function in patients with coronary artery disease. Int J Cardiol. 2019;281:35-9.
173. Tanase DM, Valasciuc E, Gosav EM, et al. Portrayal of NLRP3 inflammasome in atherosclerosis: current knowledge and therapeutic targets. Int J Mol Sci. 2023;24:8162.
174. Mankan AK, Dau T, Jenne D, Hornung V. The NLRP3/ASC/Caspase-1 axis regulates IL-1β processing in neutrophils. Eur J Immunol. 2012;42:710-5.
175. Paget C, Doz-Deblauwe E, Winter N, Briard B. Specific NLRP3 inflammasome assembling and regulation in neutrophils: relevance in inflammatory and infectious diseases. Cells. 2022;11:1188.
176. Fountoulakis PN, Theofilis P, Vlachakis PK, et al. Gut microbiota in heart failure-the role of inflammation. Biomedicines. 2025;13:911.
177. Dufour D, Khalil A, Nuyens V, et al. Native and myeloperoxidase-oxidized low-density lipoproteins act in synergy to induce release of resolvin-D1 from endothelial cells. Atherosclerosis. 2018;272:108-17.
178. Pichavaram P, Mani AM, Singh NK, Rao GN. Cholesterol crystals promote endothelial cell and monocyte interactions via H2O2-mediated PP2A inhibition, NFκB activation and ICAM1 and VCAM1 expression. Redox Biol. 2019;24:101180.
179. Varadharaj S, Kelly OJ, Khayat RN, Kumar PS, Ahmed N, Zweier JL. Role of dietary antioxidants in the preservation of vascular function and the modulation of health and disease. Front Cardiovasc Med. 2017;4:64.
180. Mortensen A, Lykkesfeldt J. Does vitamin C enhance nitric oxide bioavailability in a tetrahydrobiopterin-dependent manner? Nitric Oxide. 2014;36:51-7.
181. Paulo M, Costa DEFR, Bonaventura D, Lunardi CN, Bendhack LM. Nitric oxide donors as potential drugs for the treatment of vascular diseases due to endothelium dysfunction. Curr Pharm Des. 2020;26:3748-59.
182. Parsamanesh N, Asghari A, Sardari S, et al. Resveratrol and endothelial function: a literature review. Pharmacol Res. 2021;170:105725.
183. Ulker S, McKeown PP, Bayraktutan U. Vitamins reverse endothelial dysfunction through regulation of eNOS and NAD(P)H oxidase activities. Hypertension. 2003;41:534-9.
184. Xue HM, Yu CM, Underwood MJ, Huang JH, Yang Q. AVE3085 protects coronary endothelium from the impairment of asymmetric dimethylarginine by activation and recoupling of eNOS. Cardiovasc Drugs Ther. 2012;26:383-92.
185. Yang Q, Xue HM, Underwood MJ, Yu CM. Mechanistic studies of AVE3085 against homocysteine in endothelial protection. Cardiovasc Drugs Ther. 2013;27:511-20.
186. Yang Q, Xue HM, Wong WT, et al. AVE3085, an enhancer of endothelial nitric oxide synthase, restores endothelial function and reduces blood pressure in spontaneously hypertensive rats. Br J Pharmacol. 2011;163:1078-85.
187. Li X, Zou J, Lin A, et al. Oxidative stress, endothelial dysfunction, and N-acetylcysteine in type 2 diabetes mellitus. Antioxid Redox Signal. 2024;40:968-89.
188. Vera R, Sánchez M, Galisteo M, et al. Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats: involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity. Clin Sci. 2007;112:183-91.
189. Pottecher J, Cheisson G, Huet O, et al. β2-adrenergic agonist protects human endothelial cells from hypoxia/reoxygenation injury in vitro. Crit Care Med. 2006;34:165-72.
190. Barbato E, Herman A, Benit E, et al. Long-term effect of molsidomine, a direct nitric oxide donor, as an add-on treatment, on endothelial dysfunction in patients with stable angina pectoris undergoing percutaneous coronary intervention: results of the MEDCOR trial. Atherosclerosis. 2015;240:351-4.
191. Vera OD, Wulff H, Braun AP. Endothelial KCa channels: novel targets to reduce atherosclerosis-driven vascular dysfunction. Front Pharmacol. 2023;14:1151244.
192. Gao F, Chen J, Zhu H. A potential strategy for treating atherosclerosis: improving endothelial function via AMP-activated protein kinase. Sci China Life Sci. 2018;61:1024-9.
193. Tong X, Dang X, Liu D, et al. Exosome-derived circ_0001785 delays atherogenesis through the ceRNA network mechanism of miR-513a-5p/TGFBR3. J Nanobiotechnology. 2023;21:362.
194. Huang HC, Wang TY, Rousseau J, et al. Biomimetic nanodrug targets inflammation and suppresses YAP/TAZ to ameliorate atherosclerosis. Biomaterials. 2024;306:122505.
