{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:24:28Z","timestamp":1790997868093,"version":"4.1.0"},"reference-count":39,"publisher":"IMR Press","issue":"2","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Cardiovasc. Med."],"abstract":"<jats:p>Endothelial activation and dysfunction is an important contributor to atherosclerosis, cardiovascular diseases and cardiorenal syndrome. Endothelial dysfunction is also linked with metabolic syndrome and type II diabetes. The search for specific and sensitive biomarkers of endothelial activation and dysfunction may have important clinical implications. This review pinpoints the differences in biomarkers between endothelial activation and endothelial dysfunction in cardiovascular diseases, and then briefly describes the most relevant biomarkers of endothelial activation. Biomarkers of endothelial activation include endothelial adhesion molecules, cytokines, C-reactive protein, CD62E+\/E-selectin activated endothelial microparticles, oxidation of low density lipoproteins, asymmetric dimethylarginine and endocan. This review also presents an update on the novel biomarkers of endothelial dysfunction, such as matrix metalloproteinases (e.g., MMP-7, MMP-9), ANGPTL2, endogdlin, annexin V+ endothelial apoptotic microparticles, and serum homocysteine. Finally, this review emphasizes the limitations of biomarkers of endothelial activation and dysfunction in clinical setting.<\/jats:p>","DOI":"10.31083\/j.rcm2302073","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T20:40:01Z","timestamp":1645735201000},"source":"Crossref","is-referenced-by-count":180,"title":["Biomarkers of endothelial activation and dysfunction in cardiovascular diseases"],"prefix":"10.31083","volume":"23","author":[{"given":"Jun","family":"Zhang","sequence":"first","affiliation":[{"name":"Baylor Heart and Vascular Institute, Dallas, TX 75226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Gimbrone MA, Garc\u00eda-Carde\u00f1a G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circulation Research. 2016; 118: 620\u2013636.","DOI":"10.1161\/CIRCRESAHA.115.306301"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Baselet B, Sonveaux P, Baatout S, Aerts A. Pathological effects of ionizing radiation: endothelial activation and dysfunction. Cellular and Molecular Life Sciences. 2019; 76: 699\u2013728.","DOI":"10.1007\/s00018-018-2956-z"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Deedwania, P. C. Mechanisms of endothelial dysfunction in the metabolic syndrome. Curr. Diab. Rep. 2003; 3, 289\u2013292.","DOI":"10.1007\/s11892-003-0019-8"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Janus A, Szahidewicz-Krupska E, Mazur G, Doroszko A. Insulin Resistance and Endothelial Dysfunction Constitute a Common Therapeutic Target in Cardiometabolic Disorders. Mediators of Inflammation. 2016; 2016: 3634948.","DOI":"10.1155\/2016\/3634948"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Hayden MR. Endothelial activation and dysfunction in metabolic syndrome, type 2 diabetes and coronavirus disease 2019. Journal of International Medical Research. 2020; 48: 030006052093974.","DOI":"10.1177\/0300060520939746"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Cotran RS, Pober JS. Endothelial activation. In Simionescu N, Simionescu M (eds.) Endothelial biology in health and diseases (pp. 335\u2013347). Plenum Press: New York and London.1988.","DOI":"10.1007\/978-1-4613-0937-6_15"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Vicen M, Vitverova B, Havelek R, Blazickova K, Machacek M, Rathouska J, et al. Regulation and role of endoglin in cholesterol-induced endothelial and vascular dysfunction in vivo and in vitro. FASEB Journal. 2019; 33: 6099\u20136114.","DOI":"10.1096\/fj.201802245R"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Lundman P, Eriksson MJ, Silveira A, Hansson L, Pernow J, Ericsson C, et al. Relation of hypertriglyceridemia to plasma concentrations of biochemical markers of inflammation and endothelial activation (C-reactive protein, interleukin-6, soluble adhesion molecules, von Willebrand factor, and endothelin-1). The American Journal of Cardiology. 2003; 91: 1128\u20131131.","DOI":"10.1016\/S0002-9149(03)00165-6"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Drenjancevic I, Jukic I, Stupin A, Cosic A, Stupin M, Selthofer-Relatie. The markers of endothelial activation. 2018.","DOI":"10.5772\/intechopen.74671"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Rabelink TJ, de Boer HC, van Zonneveld AJ. Endothelial activation and circulating markers of endothelial activation in kidney disease. Nature Reviews Nephrology. 2010; 6: 404\u2013414.","DOI":"10.1038\/nrneph.2010.65"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Zhang J, Defelice AF, Hanig JP, Colatsky T. Biomarkers of endothelial cell activation serve as potential surrogate markers for drug induced vascular injury. Toxicologic Pathology. 2010; 38: 856\u2013871.","DOI":"10.1177\/0192623310378866"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Zhang J, Hanig JP, De Felice AF. Biomarkers of endothelial cell activation: candidate markers for drug-induced vasculitis in patients or drug-induced vascular injury in animals. Vascular Pharmacology. 2012; 56: 14\u201325.","DOI":"10.1016\/j.vph.2011.09.002"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Szmitko PE, Wang C, Weisel RD, de Almeida JR, Anderson TJ, Verma S. New markers of inflammation and endothelial cell activation: Part I. Circulation. 2003; 108: 1917\u20131923.","DOI":"10.1161\/01.CIR.0000089190.95415.9F"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Hwang SJ, Ballantyne CM, Sharrett AR, Smith LC, Davis CE, Gotto AM, et al. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk in Communities (ARiC) study. Circulation. 1997; 96: 4219\u20134225.","DOI":"10.1161\/01.CIR.96.12.4219"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Tzoulaki I, Murray GD, Lee AJ, Rumley A, Lowe GDO, Fowkes FGR. C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh Artery Study. Circulation. 2005; 112: 976\u2013983.","DOI":"10.1161\/CIRCULATIONAHA.104.513085"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Cui Y, Zheng L, Jiang M, Jia R, Zhang X, Quan Q, et al. Circulating microparticles in patients with coronary heart disease and its correlation with interleukin-6 and C-reactive protein. Molecular Biology Reports. 2013; 40: 6437\u20136442.","DOI":"10.1007\/s11033-013-2758-1"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"E. Berezin A. Impaired Phenotype of Circulating Endothelial-Derived Microparticles: Novel Marker of Cardiovascular Risk. Journal of Cardiology and Therapy. 2015; 2: 365\u2013370.","DOI":"10.17554\/j.issn.2309-6861.2015.02.78"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Hu S, Zhang H, Zhang Q, Xiu R. Small-size circulating endothelial microparticles in coronary artery disease. PLoS ONE. 2014; 9: e104528.","DOI":"10.1371\/journal.pone.0104528"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Landers\u2010Ramos RQ, Addison OA, Beamer B, Katzel LI, Blumenthal JB, Robinson S, et al. Circulating microparticle concentrations across acute and chronic cardiovascular disease conditions. Physiological Reports. 2020; 15: e14534","DOI":"10.14814\/phy2.14534"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Tadzic R, Mihalj M, Vcev A, Ennen J, Tadzic A, Drenjancevic I. The effects of arterial blood pressure reduction on endocan and soluble endothelial cell adhesion molecules (CAMs) and CAMs ligands expression in hypertensive patients on Ca-channel blocker therapy. Kidney & Blood Pressure Research. 2013; 37: 103\u2013115.","DOI":"10.1159\/000350064"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Boumiza S, Chahed K, Tabka Z, Jacob M, Norel X, Ozen G. MMPs and TIMPs levels are correlated with anthropometric parameters, blood pressure, and endothelial function in obesity. Scientific Reports. 2021; 11: 20052.","DOI":"10.1038\/s41598-021-99577-2"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Olejarz W, \u0141acheta D, Ubiak-Tomaszewska G. Matrix metalloproteinases as biomarkers of atherosclerotic plaque instability. International Journal of Molecular Sciences. 2020; 21: 3946.","DOI":"10.3390\/ijms21113946"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Horio E, Kadomatsu T, Miyata K, Arai Y, Hosokawa K, Doi Y, et al. Role of endothelial cell-derived angptl2 in vascular inflammation leading to endothelial dysfunction and atherosclerosis progression. Arteriosclerosis, Thrombosis, and Vascular Biology. 2014; 34: 790\u2013800.","DOI":"10.1161\/ATVBAHA.113.303116"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Hata J, Mukai N, Nagata M, Ohara T, Yoshida D, Kishimoto H, et al. Serum Angiopoietin\u2013Like Protein 2 is a Novel Risk Factor for Cardiovascular Disease in the Community. Arteriosclerosis, Thrombosis, and Vascular Biology. 2016; 36: 1686\u20131691.","DOI":"10.1161\/ATVBAHA.116.307291"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Rathouska J, Jezkova K, Nemeckova I, Nachtigal P. Soluble endoglin, hypercholesterolemia and endothelial dysfunction. Atherosclerosis. 2015; 243: 383\u2013388.","DOI":"10.1016\/j.atherosclerosis.2015.10.003"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Rathouska J, Vecerova L, Strasky Z, Slanarova M, Brcakova E, Mullerova Z, et al. Endoglin as a possible marker of atorvastatin treatment benefit in atherosclerosis. Pharmacological Research. 2011; 64: 53\u201359.","DOI":"10.1016\/j.phrs.2011.03.008"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. British Medical Journal. 2002; 325: 1202.","DOI":"10.1136\/bmj.325.7374.1202"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Qin X, Li Y, Sun N, Wang H, Zhang Y, Wang J, et al. Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients. Arteriosclerosis, Thrombosis, and Vascular Biology. 2017; 37: 166\u2013172.","DOI":"10.1161\/ATVBAHA.116.308515"},{"key":"ref29","unstructured":"Rogula S, G\u0105secka A, Filipiak KJ. Macroscopic role of microparticles in cardiovascular disease. Polski Merkuriusz Lekarski. 2020; 49: 255\u2013259."},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Strasky Z, Vecerova L, Rathouska J, Slanarova M, Brcakova E, Kudlackova Z, et al. Cholesterol effects on endoglin and its downstream pathways in ApoE\/LDLR double knockout mice. Circulation Journal. 2011; 75: 1747\u20131755.","DOI":"10.1253\/circj.CJ-10-1285"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Huang A, Pinto JT, Froogh G, Kandhi S, Qin J, Wolin MS, et al. Role of homocysteinylation of ACE in endothelial dysfunction of arteries. American Journal of Physiology-Heart and Circulatory Physiology. 2015; 308: H92\u2013H100.","DOI":"10.1152\/ajpheart.00577.2014"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Fink K, Feldbr\u00fcgge L, Schwarz M, Bourgeois N, Helbing T, Bode C, et al. Circulating annexin V positive microparticles in patients after successful cardiopulmonary resuscitation. Critical Care. 2011; 15: R251.","DOI":"10.1186\/cc10512"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Werner N, Wassmann S, Ahlers P, Kosiol S, Nickenig G. Circulating CD31+\/annexin V+ apoptotic microparticles correlate with coronary endothelial function in patients with coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 2006; 26: 112\u2013116.","DOI":"10.1161\/01.ATV.0000191634.13057.15"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Sinning J-M, Losch J, Walenta K, B\u0151hm M, Nickenig G, Werner N. Circulating CD311\/Annexin V microparticles correlate with cardiovascular outcomes. European Heart Journal. 2011; 32: 2034\u20132041.","DOI":"10.1093\/eurheartj\/ehq478"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Zahran AM, Sayed SK, Abd El Hafeez HA, Khalifa WA, Mohamed NA, Hetta HF. Circulating microparticle subpopulation in metabolic syndrome: relation to oxidative stress and coagulation markers. Diabetes, Metabolic Syndrome and Obesity. 2019; 12: 485\u2013493.","DOI":"10.2147\/DMSO.S191750"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Ardoin SP, Shanahan JC, Pisetsky DS. The role of microparticles in inflammation and thrombosis. Scandinavian Journal of Immunology. 2007; 66: 159\u2013165.","DOI":"10.1111\/j.1365-3083.2007.01984.x"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Barteneva NS, Fasler-Kan E, Bernimoulin M, Stern JNH, Ponomarev ED, Duckett L, et al. Circulating microparticles: square the circle. 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