Endothelial cell dysfunction as a novel therapeutic target in atherosclerosis

References

• Cahill PA, Redmond EM. Vascular endothelium - Gatekeeper of vessel health. Atherosclerosis. 2016;248:97–109.
   PubMed Web of Science ®Google Scholar
• Kasprzak JD, Klosinska M, Drozdz J. Clinical aspects of assessment of endothelial function. Pharmacological Reports: PR. 2006;58(Suppl)33–40.
   PubMedGoogle Scholar
• Xiong Y, Hla T. S1P control of endothelial integrity. Curr Top Microbiol Immunol. 2014;378:85–105.
   PubMed Web of Science ®Google Scholar
• Triggle CR, Samuel SM, Ravishankar S, et al. The endothelium: influencing vascular smooth muscle in many ways. Can J Physiol Pharmacol. 2012;90(6):713–738.
   PubMed Web of Science ®Google Scholar
• Morel DW, DiCorleto PE, Chisolm GM. Endothelial and smooth muscle cells alter low density lipoprotein in vitro by free radical oxidation. Arteriosclerosis (Dallas, Tex). 1984;4(4):357–364.
   PubMedGoogle Scholar
• Steinbrecher UP, Parthasarathy S, Leake DS, et al. Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A. 1984;81(12):3883–3887.
   PubMed Web of Science ®Google Scholar
• Mitra S, Goyal T, Mehta JL. Oxidized LDL, LOX-1 and Atherosclerosis. Cardiovasc Drugs Ther. 2011;25(5):419–429.
   PubMed Web of Science ®Google Scholar
• Esper RJ, Nordaby RA, Vilarino JO, et al. Endothelial dysfunction: a comprehensive appraisal. Cardiovasc Diabetol. 2006;5:4.
   PubMed Web of Science ®Google Scholar
• Breton-Romero R, Acin-Perez R, Rodriguez-Pascual F, et al. Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells. Biochim Biophys Acta. 2014;1843(11):2403–2413.
   PubMed Web of Science ®Google Scholar
• Antoniades C, Bakogiannis C, Leeson P, et al. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation. 2011;124(3):335–345.
   PubMed Web of Science ®Google Scholar
• Tousoulis D, Psaltopoulou T, Androulakis E, et al. Oxidative stress and early atherosclerosis: novel antioxidant treatment. Cardiovasc Drugs Therapy /Sponsored by Int Soc Cardiovasc Pharmacother. 2015;29(1):75–88.
   PubMed Web of Science ®Google Scholar
• Pirs M, Jug B, Erzen B, et al. Relationship between markers of endothelial dysfunction and inflammation and subclinical atherosclerosis in HIV-infected male patients below 55 years of age. Acta Dermatovenerologica Alpina, Pannonica, Et Adriatica. 2014;23(3):49–52.
   PubMedGoogle Scholar
• Choi BJ, Matsuo Y, Aoki T, et al. Coronary endothelial dysfunction is associated with inflammation and vasa vasorum proliferation in patients with early atherosclerosis. Arterioscler Thromb Vasc Biol. 2014;34(11):2473–2477.
   PubMed Web of Science ®Google Scholar
• Martin BJ, Anderson TJ. Risk prediction in cardiovascular disease: the prognostic significance of endothelial dysfunction. Can J Cardiol. 2009;25(Suppl A):15a–20a.
   Google Scholar
• Halcox JP, Schenke WH, Zalos G, et al. Prognostic value of coronary vascular endothelial dysfunction. Circulation. 2002;106(6):653–658.
   PubMed Web of Science ®Google Scholar
• Frolow M, Drozdz A, Kowalewska A, et al. Comprehensive assessment of vascular health in patients; towards endothelium-guided therapy. Pharmacological Reports: PR. 2015;67(4):786–792.
   PubMed Web of Science ®Google Scholar
• Flammer AJ, Anderson T, Celermajer DS, et al. The assessment of endothelial function: from research into clinical practice. Circulation. 2012;126(6):753–767.
   PubMed Web of Science ®Google Scholar
• Boger RH, Cooke JP, Vallance P. ADMA: an emerging cardiovascular risk factor. Vasc Med. 2005;10(Suppl 1):S1–2.
   Google Scholar
• Park KH, Park WJ. Endothelial Dysfunction: Clinical Implications in Cardiovascular Disease and Therapeutic Approaches. J Korean Med Sci. 2015;30(9):1213–1225.
   PubMed Web of Science ®Google Scholar
• Gradinaru D, Borsa C, Ionescu C, et al. Oxidized LDL and NO synthesis–Biomarkers of endothelial dysfunction and ageing. Mech Ageing Dev. 2015;151:101–113.
   PubMed Web of Science ®Google Scholar
• Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovasc Res. 2005;66(2):286–294.
   PubMed Web of Science ®Google Scholar
• Merchant N, Searles CD, Pandian A, et al. Nebivolol in high-risk, obese African Americans with stage 1 hypertension: effects on blood pressure, vascular compliance, and endothelial function. J Clin Hypertens (Greenwich, Conn). 2009;11(12):720–725.
   PubMed Web of Science ®Google Scholar
• Evangelista S, Garbin U, Pasini AF, et al. Effect of DL-nebivolol, its enantiomers and metabolites on the intracellular production of superoxide and nitric oxide in human endothelial cells. Pharmacol Res. 2007;55(4):303–309.
   PubMed Web of Science ®Google Scholar
• Akcay A, Acar G, Kurutas E, et al. Beneficial effects of nebivolol treatment on oxidative stress parameters in patients with slow coronary flow. Turk Kardiyoloji Dernegi Arsivi: Turk Kardiyoloji Derneginin Yayin Organidir. 2010;38(4):244–249.
   PubMedGoogle Scholar
• Hollenberg NK. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. Curr Hypertens Rep. 2003;5(3):183–185.
   PubMedGoogle Scholar
• Cardillo C, Campia U, Iantorno M, et al. Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive patients. Hypertension. 2004;43(1):36–40.
   PubMed Web of Science ®Google Scholar
• Traupe T, Lang M, Goettsch W, et al. Obesity increases prostanoid-mediated vasoconstriction and vascular thromboxane receptor gene expression. J Hypertens. 2002;20(11):2239–2245.
   PubMed Web of Science ®Google Scholar
• Gao WQ, Feng QZ, Li YF, et al. Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound. BMC Cardiovasc Disord. 2014;14:60.
   PubMed Web of Science ®Google Scholar
• Tousoulis D, Oikonomou E, Siasos G, et al. Dose-dependent effects of short term atorvastatin treatment on arterial wall properties and on indices of left ventricular remodeling in ischemic heart failure. Atherosclerosis. 2013;227(2):367–372.
   PubMed Web of Science ®Google Scholar
• Nohara R, Daida H, Hata M, et al. Effect of long-term intensive lipid-lowering therapy with rosuvastatin on progression of carotid intima-media thickness–Justification for Atherosclerosis Regression Treatment (JART) extension study. Circ J: Off J Jpn Circ Soc. 2013;77(6):1526–1533.
   PubMed Web of Science ®Google Scholar
• Kovarnik T, Mintz GS, Skalicka H, et al. Virtual histology evaluation of atherosclerosis regression during atorvastatin and ezetimibe administration: HEAVEN study. Circ J: Off J Jpn Circ Soc. 2012;76(1):176–183.
   PubMed Web of Science ®Google Scholar
• Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285(13):1711–1718.
   PubMed Web of Science ®Google Scholar
• Kim JS, Kim J, Choi D, et al. Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial. JACC Cardiovasc Interventions. 2010;3(3):332–339.
   PubMed Web of Science ®Google Scholar
• Oz F, Cizgici AY, Oflaz H, et al. Impact of vitamin D insufficiency on the epicardial coronary flow velocity and endothelial function. Coron Artery Dis. 2013;24(5):392–397.
   PubMed Web of Science ®Google Scholar
• Hirata M, Serizawa K, Aizawa K, et al. 22-Oxacalcitriol prevents progression of endothelial dysfunction through antioxidative effects in rats with type 2 diabetes and early-stage nephropathy. Nephrol Dialysis, Transplant: Off Publ Eur Dialysis Transplant Assoc - Eur Renal Assoc. 2013;28(5):1166–1174.
   Google Scholar
• Pashkow FJ. Oxidative stress and inflammation in heart disease: do antioxidants have a role in treatment and/or prevention?. Int J Inflam. 2011;2011:514623.
   PubMedGoogle Scholar
• Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet (London, England). 1996;347(9004):781–786.
   PubMed Web of Science ®Google Scholar
• Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354(15):1578–1588.
   PubMed Web of Science ®Google Scholar
• Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004;291(5):565–575.
   PubMed Web of Science ®Google Scholar
• Avogaro A, de Kreutzenberg SV, Fadini G. Endothelial dysfunction: causes and consequences in patients with diabetes mellitus. Diabetes Res Clin Pract. 2008;82(Suppl 2):S94–s101.
   PubMed Web of Science ®Google Scholar
• Title LM, Cummings PM, Giddens K, et al. Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E. J Am Coll Cardiol. 2000;36(7):2185–2191.
   PubMed Web of Science ®Google Scholar
• Johnstone MT, Creager SJ, Scales KM, et al. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation. 1993;88(6):2510–2516.
   PubMed Web of Science ®Google Scholar
• Dubo S, Gallegos D, Cabrera L, et al. Cardiovascular action of insulin in health and disease: endothelial L-arginine transport and cardiac voltage-dependent potassium channels. Front Physiol. 2016;7:74.
   PubMed Web of Science ®Google Scholar
• Tomczynska M, Bijak M, Saluk J. Metformin - the drug for the treatment of autoimmune diseases; a new use of a known anti-diabetic drug. Curr Top Med Chem. 2016;16(19):2223–2230.
   PubMedGoogle Scholar
• Ghosh S, Lakshmanan AP, Hwang MJ, et al. Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic conditions. Biochem Pharmacol. 2015;98(3):412–421.
   PubMed Web of Science ®Google Scholar
• Triggle CR, Ding H. Metformin is not just an antihyperglycaemic drug but also has protective effects on the vascular endothelium. Acta Physiol (Oxf). 2015. doi:10.1111/apha.12644 [Epub ahead of print]
   PubMedGoogle Scholar
• Mineo C, Deguchi H, Griffin JH, et al. Endothelial and antithrombotic actions of HDL. Circ Res. 2006;98(11):1352–1364.
   PubMed Web of Science ®Google Scholar
• Anderson TJ, Meredith IT, Yeung AC, et al. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med. 1995;332(8):488–493.
   PubMed Web of Science ®Google Scholar
• Bonetti PO, Lerman LO, Napoli C, et al. Statin effects beyond lipid lowering–are they clinically relevant? Eur Heart J. 2003;24(3):225–248.
   PubMed Web of Science ®Google Scholar
• Kirmizis D, Papagianni A, Dogrammatzi F, et al. Effects of simvastatin on markers of inflammation, oxidative stress and endothelial cell apoptosis in patients on chronic hemodialysis. J Atheroscler Thromb. 2010;17(12):1256–1265.
   PubMed Web of Science ®Google Scholar
• Laufs U, La Fata V, Plutzky J, et al. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97(12):1129–1135.
   PubMed Web of Science ®Google Scholar
• Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109(23 Suppl 1):Iii27–32.
   PubMed Web of Science ®Google Scholar
• Mehta JL, Li DY, Chen HJ, et al. Inhibition of LOX-1 by statins may relate to upregulation of eNOS. Biochem Biophys Res Commun. 2001;289(4):857–861.
   PubMed Web of Science ®Google Scholar
• Reriani MK, Dunlay SM, Gupta B, et al. Effects of statins on coronary and peripheral endothelial function in humans: a systematic review and meta-analysis of randomized controlled trials. Eur J Cardiovasc Prev Rehabil: Off J Eur Soc Cardiol, Working Groups Epidemiol Prev and Cardiac Rehabil Exercise Physiol. 2011;18(5):704–716.
   PubMedGoogle Scholar
• Vanhoutte PM, Shimokawa H, Feletou M, et al. Endothelial dysfunction and vascular disease - a thirthieth anniversary update. Acta Physiol (Oxf). 2015. doi:10.1111/apha.12646. [Epub ahead of print]
   Google Scholar
• Tang EH, Vanhoutte PM. Endothelial dysfunction: a strategic target in the treatment of hypertension? Pflugers Archiv: European Journal of Physiology. 2010;459(6):995–1004.
   PubMed Web of Science ®Google Scholar
• Sola S, Mir MQ, Cheema FA, et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study. Circulation. 2005;111(3):343–348.
   PubMed Web of Science ®Google Scholar
• Shahin Y, Khan JA, Samuel N, et al. Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials. Atherosclerosis. 2011;216(1):7–16.
   PubMed Web of Science ®Google Scholar
• Rajagopalan S, Harrison DG. Reversing endothelial dysfunction with ACE inhibitors. A New Trend. Circulation. 1996;94(3):240–243.
   PubMed Web of Science ®Google Scholar
• Imanishi T, Tsujioka H, Ikejima H, et al. Renin inhibitor aliskiren improves impaired nitric oxide bioavailability and protects against atherosclerotic changes. Hypertension. 2008;52(3):563–572.
   PubMed Web of Science ®Google Scholar
• Chou CL, Pang CY, Lee TJ, et al. Direct renin inhibitor prevents and ameliorates insulin resistance, aortic endothelial dysfunction and vascular remodeling in fructose-fed hypertensive rats. Hypertens Res Offi J Jpn Soc Hypertens. 2013;36(2):123–128.
   Web of Science ®Google Scholar
• Khan MU, Zhao W, Zhao T, et al. Nebivolol: a multifaceted antioxidant and cardioprotectant in hypertensive heart disease. J Cardiovasc Pharmacol. 2013;62(5):445–451.
   PubMed Web of Science ®Google Scholar
• Kalinowski L, Dobrucki LW, Szczepanska-Konkel M, et al. Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action. Circulation. 2003;107(21):2747–2752.
   PubMed Web of Science ®Google Scholar
• Bank AJ, Kelly AS, Thelen AM, et al. Effects of carvedilol versus metoprolol on endothelial function and oxidative stress in patients with type 2 diabetes mellitus. Am J Hypertens. 2007;20(7):777–783.
   PubMed Web of Science ®Google Scholar
• Wassmann S, Nickenig G. Interrelationship of free oxygen radicals and endothelial dysfunction–modulation by statins. Endothelium: J Endothelial Cell Res. 2003;10(1):23–33.
   PubMed Web of Science ®Google Scholar
• Burke A, Fitzgerald GA. Oxidative stress and smoking-induced vascular injury. Prog Cardiovasc Dis. 2003;46(1):79–90.
   PubMed Web of Science ®Google Scholar
• Ostadal P. Statins as first-line therapy for acute coronary syndrome? Exp Clin Cardiol. 2012;17(4):227–236.
   PubMedGoogle Scholar
• Milionis HJ, Liberopoulos EN, Elisaf MS, et al. Analysis of antihypertensive effects of statins. Curr Hypertens Rep. 2007;9(3):175–183.
   PubMed Web of Science ®Google Scholar
• Inoue T, Takayanagi K, Hayashi T, et al. Fluvastatin attenuates nitrate tolerance in patients with ischemic heart disease complicating hypercholesterolemia. Int J Cardiol. 2003;90(2–3):181–188.
   PubMed Web of Science ®Google Scholar
• Mehta JL, editor. Inflammatory and infectious basis of atherosclerosis. Basel: Birkhäuser Biosciences; 2001.
   Google Scholar
• Torzewski M, Rist C, Mortensen RF, et al. C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler Thromb Vasc Biol. 2000;20(9):2094–2099.
   PubMed Web of Science ®Google Scholar
• Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med. 1999;340(2):115–126.
   PubMed Web of Science ®Google Scholar
• Back M, Weber C, Lutgens E. Regulation of atherosclerotic plaque inflammation. J Intern Med. 2015;278(5):462–482.
   PubMed Web of Science ®Google Scholar
• Back M, Hansson GK. Anti-inflammatory therapies for atherosclerosis. Nat Reviews Cardiol. 2015;12(4):199–211.
   PubMed Web of Science ®Google Scholar
• Salisbury D, Bronas U. Inflammation and immune system contribution to the etiology of atherosclerosis: mechanisms and methods of assessment. Nurs Res. 2014;63(5):375–385.
   PubMed Web of Science ®Google Scholar
• Mehta JL, Li DY. Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells. Biochem Biophys Res Commun. 1998;248(3):511–514.
   PubMed Web of Science ®Google Scholar
• Dandapat A, Hu C, Sun L, et al. Small concentrations of oxLDL induce capillary tube formation from endothelial cells via LOX-1-dependent redox-sensitive pathway. Arterioscler Thromb Vasc Biol. 2007;27(11):2435–2442.
   PubMed Web of Science ®Google Scholar
• Wang X, Khaidakov M, Ding Z, et al. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and cardiac fibroblast growth. Hypertension. 2012;60(6):1437–1442.
   PubMed Web of Science ®Google Scholar
• Mehta JL, Khaidakov M, Hermonat PL, et al. LOX-1: a new target for therapy for cardiovascular diseases. Cardiovasc Drugs Therapy /Sponsored by Int Soc Cardiovasc Pharmacother. 2011;25(5):495–500.
   PubMed Web of Science ®Google Scholar
• Moss JW, Ramji DP. Interferon-gamma: promising therapeutic target in atherosclerosis. World J Exp Med. 2015;5(3):154–159.
   PubMedGoogle Scholar
• Gotsman I, Lichtman AH. Targeting interferon-gamma to treat atherosclerosis. Circ Res. 2007;101(4):333–334.
   PubMed Web of Science ®Google Scholar
• Petros RA, DeSimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discovery. 2010;9(8):615–627.
   PubMed Web of Science ®Google Scholar
• Mitchell A, Fujisawa T, Newby D, et al. Vascular injury and repair: a potential target for cell therapies. Future Cardiol. 2015;11(1):45–60.
   PubMedGoogle Scholar
• Sohy D, Yano H, de Nadai P, et al. Hetero-oligomerization of CCR2, CCR5, and CXCR4 and the protean effects of “selective” antagonists. J Biol Chem. 2009;284(45):31270–31279.
   PubMed Web of Science ®Google Scholar
• van Wanrooij EJ, Happe H, Hauer AD, et al. HIV entry inhibitor TAK-779 attenuates atherogenesis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2005;25(12):2642–2647.
   PubMed Web of Science ®Google Scholar
• Copin JC, Da Silva RF, Fraga-Silva RA, et al. Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 2013;33(4):490–498.
   PubMed Web of Science ®Google Scholar
• Koenen RR, von Hundelshausen P, Nesmelova IV, et al. Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice. Nat Med. 2009;15(1):97–103.
   PubMed Web of Science ®Google Scholar
• Gilbert J, Lekstrom-Himes J, Donaldson D, et al. Effect of CC chemokine receptor 2 CCR2 blockade on serum C-reactive protein in individuals at atherosclerotic risk and with a single nucleotide polymorphism of the monocyte chemoattractant protein-1 promoter region. Am J Cardiol. 2011;107(6):906–911.
   PubMed Web of Science ®Google Scholar
• Back M, Sultan A, Ovchinnikova O, et al. 5-Lipoxygenase-activating protein: a potential link between innate and adaptive immunity in atherosclerosis and adipose tissue inflammation. Circ Res. 2007;100(7):946–949.
   PubMed Web of Science ®Google Scholar
• Hakonarson H, Thorvaldsson S, Helgadottir A, et al. Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA. 2005;293(18):2245–2256.
   PubMed Web of Science ®Google Scholar
• Tardif JC, L’Allier PL, Ibrahim R, et al. Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome. Circ Cardiovasc Imaging. 2010;3(3):298–307.
   PubMed Web of Science ®Google Scholar
• Hlawaty H, Jacob MP, Louedec L, et al. Leukotriene receptor antagonism and the prevention of extracellular matrix degradation during atherosclerosis and in-stent stenosis. Arterioscler Thromb Vasc Biol. 2009;29(4):518–524.
   PubMed Web of Science ®Google Scholar
• Allayee H, Hartiala J, Lee W, et al. The effect of montelukast and low-dose theophylline on cardiovascular disease risk factors in asthmatics. Chest. 2007;132(3):868–874.
   PubMed Web of Science ®Google Scholar
• Ingelsson E, Yin L, Back M. Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease. J Allergy Clin Immunol. 2012;129(3):702–7.e2.
   PubMed Web of Science ®Google Scholar
• Genovese MC, Becker JC, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005;353(11):1114–1123.
   PubMed Web of Science ®Google Scholar
• Doesch AO, Zhao L, Gleissner CA, et al. Inhibition of B7-1 (CD80) by RhuDex(R) reduces lipopolysaccharide-mediated inflammation in human atherosclerotic lesions. Drug Des Devel Ther. 2014;8:447–457.
   PubMed Web of Science ®Google Scholar
• Peters AL, Stunz LL, Bishop GA. CD40 and autoimmunity: the dark side of a great activator. Semin Immunol. 2009;21(5):293–300.
   PubMed Web of Science ®Google Scholar
• Liossis SN, Sfikakis PP. Costimulation blockade in the treatment of rheumatic diseases. Biodrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. 2004;18(2):95–102.
   PubMed Web of Science ®Google Scholar
• Kanmaz T, Fechner JJ Jr., Torrealba J, et al. Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model. Transplantation. 2004;77(6):914–920.
   PubMed Web of Science ®Google Scholar
• Breton-Romero R, Feng B, Holbrook M, et al. Endothelial dysfunction in human diabetes is mediated by Wnt5a-JNK signaling. Arterioscler Thromb Vasc Biol. 2016;36(3):561–569.
   PubMed Web of Science ®Google Scholar
• Steyers CM, Miller FJ. Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci. 2014;15(7):11324–11349.
   PubMed Web of Science ®Google Scholar
• Graff JW, Dickson AM, Clay G, et al. Identifying functional microRNAs in macrophages with polarized phenotypes. J Biol Chem. 2012;287(26):21816–21825.
   PubMed Web of Science ®Google Scholar
• Androulidaki A, Iliopoulos D, Arranz A, et al. The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity. 2009;31(2):220–231.
   PubMed Web of Science ®Google Scholar
• Lu LF, Thai TH, Calado DP, et al. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity. 2009;30(1):80–91.
   PubMed Web of Science ®Google Scholar
• Kumar S, Kim CW, Simmons RD, et al. Role of flow-sensitive microRNAs in endothelial dysfunction and atherosclerosis: mechanosensitive athero-miRs. Arterioscler Thromb Vasc Biol. 2014;34(10):2206–2216.
   PubMed Web of Science ®Google Scholar
• Ma S, Tian XY, Zhang Y, et al. E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis. Sci Rep. 2016;6:22910.
   PubMed Web of Science ®Google Scholar
• Dunn J, Thabet S, Jo H. Flow-dependent epigenetic DNA methylation in endothelial gene expression and atherosclerosis. Arterioscler Thromb Vasc Biol. 2015;35(7):1562–1569.
   PubMed Web of Science ®Google Scholar
• Poss J, Werner C, Lorenz D, et al. The renin inhibitor aliskiren upregulates pro-angiogenic cells and reduces atherogenesis in mice. Basic Res Cardiol. 2010;105(6):725–735.
   PubMed Web of Science ®Google Scholar
• Desideri G, Grassi D, Croce G, et al. Different effects of angiotensin converting enzyme inhibitors on endothelin-1 and nitric oxide balance in human vascular endothelial cells: evidence of an oxidant-sensitive pathway. Mediators Inflamm. 2008;2008:305087.
   PubMed Web of Science ®Google Scholar
• Tsai KL, Huang YH, Kao CL, et al. A novel mechanism of coenzyme Q10 protects against human endothelial cells from oxidative stress-induced injury by modulating NO-related pathways. J Nutr Biochem. 2012;23(5):458–468.
   PubMed Web of Science ®Google Scholar
• Thakkar S, Wang X, Khaidakov M, et al. Structure-based design targeted at LOX-1, a receptor for oxidized low-density lipoprotein. Sci Rep. 2015;5:16740.
   PubMed Web of Science ®Google Scholar
• Lasala GP, Silva JA, Gardner PA, et al. Combination stem cell therapy for the treatment of severe limb ischemia: safety and efficacy analysis. Angiology. 2010;61(6):551–556.
   PubMed Web of Science ®Google Scholar
• Losordo DW, Henry TD, Davidson C, et al. Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res. 2011;109(4):428–436.
   PubMed Web of Science ®Google Scholar
• Lasala GP, Silva JA, Kusnick BA, et al. Combination stem cell therapy for the treatment of medically refractory coronary ischemia: a Phase I study. Cardiovascular Revascularization Medicine: Including Molecular Interventions. 2011;12(1):29–34.
   PubMedGoogle Scholar
• Erbs S, Linke A, Adams V, et al. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study. Circ Res. 2005;97(8):756–762.
   PubMed Web of Science ®Google Scholar
• Boyle AJ, Whitbourn R, Schlicht S, et al. Intra-coronary high-dose CD34+ stem cells in patients with chronic ischemic heart disease: a 12-month follow-up. Int J Cardiol. 2006;109(1):21–27.
   PubMed Web of Science ®Google Scholar
• de Jager SC, Kuiper J. Vaccination strategies in atherosclerosis. Thromb Haemost. 2011;106(5):796–803.
   PubMed Web of Science ®Google Scholar
• Sonkoly E, Stahle M, Pivarcsi A. MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation. Semin Cancer Biol. 2008;18(2):131–140.
   PubMed Web of Science ®Google Scholar
• Samanta S, Balasubramanian S, Rajasingh S, et al. MicroRNA: A new therapeutic strategy for cardiovascular diseases. Trends Cardiovasc Med. 2016;26(5):407–419.
   Google Scholar
• Grimson A, Farh KK, Johnston WK, et al. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007;27(1):91–105.
   PubMed Web of Science ®Google Scholar
• Dai Y, Zhang Z, Cao Y, et al. MiR-590-5p inhibits oxidized- LDL induced angiogenesis by targeting LOX-1. Sci Rep. 2016;6:22607.
   PubMed Web of Science ®Google Scholar
• Creemers EE, Tijsen AJ, Pinto YM. Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res. 2012;110(3):483–495.
   PubMed Web of Science ®Google Scholar
• Quiat D, Olson EN. MicroRNAs in cardiovascular disease: from pathogenesis to prevention and treatment. J Clin Invest. 2013;123(1):11–18.
   PubMed Web of Science ®Google Scholar
• Sucharov C, Bristow MR, Port JD. miRNA expression in the failing human heart: functional correlates. J Mol Cell Cardiol. 2008;45(2):185–192.
   PubMed Web of Science ®Google Scholar
• Garcia-Gonzalez V, Delgado-Coello B, Perez-Torres A, et al. Reality of a vaccine in the prevention and treatment of atherosclerosis. Arch Med Res. 2015;46(5):427–437.
   PubMed Web of Science ®Google Scholar
• Ait-Oufella H, Sage AP, Mallat Z, et al. Adaptive (T and B cells) immunity and control by dendritic cells in atherosclerosis. Circ Res. 2014;114(10):1640–1660.
   PubMed Web of Science ®Google Scholar
• Fredrikson GN, Andersson L, Söderberg I, et al. Atheroprotective immunization with MDA-modified apo B-100 peptide sequences is associated with activation of Th2 specific antibody expression. Autoimmunity. 2005;38(2):171–179.
   PubMed Web of Science ®Google Scholar
• Fredrikson GN, Björkbacka H, Söderberg I, et al. Treatment with apo B peptide vaccines inhibits atherosclerosis in human apo B-100 transgenic mice without inducing an increase in peptide-specific antibodies. J Intern Med. 2008;264(6):563–570.
   PubMed Web of Science ®Google Scholar
• Andreou I, Antoniadis AP, Shishido K, et al. How do we prevent the vulnerable atherosclerotic plaque from rupturing? Insights from in vivo assessments of plaque, vascular remodeling, and local endothelial shear stress. J Cardiovasc Pharmacol Ther. 2015;20(3):261–275.
   PubMed Web of Science ®Google Scholar
• Gimbrone MA Jr., Topper JN, Nagel T, et al., Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci. 2000;902:230–239. discussion 9-40
   PubMed Web of Science ®Google Scholar
• Chistiakov DA, Orekhov AN, Bobryshev YV. Effects of shear stress on endothelial cells: go with the flow. Acta Physiol (Oxf). 2016. doi:10.1111/apha.12725. [Epub ahead of print]
   PubMedGoogle Scholar
• Pahakis MY, Kosky JR, Dull RO, et al. The role of endothelial glycocalyx components in mechanotransduction of fluid shear stress. Biochem Biophys Res Commun. 2007;355(1):228–233.
   PubMed Web of Science ®Google Scholar
• White SJ, Hayes EM, Lehoux S, et al. Characterization of the differential response of endothelial cells exposed to normal and elevated laminar shear stress. J Cell Physiol. 2011;226(11):2841–2848.
   PubMed Web of Science ®Google Scholar
• Fukumoto Y, Hiro T, Fujii T, et al. Localized elevation of shear stress is related to coronary plaque rupture: a 3-dimensional intravascular ultrasound study with in-vivo color mapping of shear stress distribution. J Am Coll Cardiol. 2008;51(6):645–650.
   PubMed Web of Science ®Google Scholar
• Liu P, Zhou B, Gu D, et al. Endothelial progenitor cell therapy in atherosclerosis: a double-edged sword? Ageing Res Rev. 2009;8(2):83–93.
   PubMed Web of Science ®Google Scholar
• Devaraj S, Jialal I. Dysfunctional endothelial progenitor cells in metabolic syndrome. Exp Diabetes Res. 2012;2012:585018.
   PubMedGoogle Scholar
• Fadini GP, Agostini C, Avogaro A. Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis. 2010;209(1):10–17.
   PubMed Web of Science ®Google Scholar
• Zhang N, Xie X, Chen H, et al. Stem cell-based therapies for atherosclerosis: perspectives and ongoing controversies. Stem Cells Dev. 2014;23(15):1731–1740.
   PubMed Web of Science ®Google Scholar
• Tang Z, Wang A, Yuan F, et al. Differentiation of multipotent vascular stem cells contributes to vascular diseases. Nat Commun. 2012;3:875.
   PubMed Web of Science ®Google Scholar
• Lao KH, Zeng L, Xu Q. Endothelial and smooth muscle cell transformation in atherosclerosis. Curr Opin Lipidol. 2015;26(5):449–456.
   PubMed Web of Science ®Google Scholar
• Ma KL, Liu J, Ni J, et al. Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed apolipoprotein e knockout mice via endothelial-mesenchymal transition. Int J Med Sci. 2013;10(4):420–426.
   PubMed Web of Science ®Google Scholar
• Chen PY, Qin L, Baeyens N, et al. Endothelial-to-mesenchymal transition drives atherosclerosis progression. J Clin Invest. 2015;125(12):4514–4528.
   PubMed Web of Science ®Google Scholar
• Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373–376.
   PubMed Web of Science ®Google Scholar
• Saxe JG. The poems of John Godfrey Saxe. Boston (MA): James R. Osgood and Co.; 1873.
   Google Scholar
• Aird WC. Spatial and temporal dynamics of the endothelium. Jth. 2005;3(7):1392–1406.
   Google Scholar
• Yepuri G, Sukhovershin R, Nazari-Shafti TZ, et al. proton pump inhibitors accelerate endothelial senescence. Circ Res. 2016;118(12):e36–e42
   PubMed Web of Science ®Google Scholar