Biomarkers of endothelial activation and dysfunction in cardiovascular diseases.

Jun Zhang

doi:10.31083/j.rcm2302073

Abstract

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.

Highlights

Endothelial activation and dysfunction is an important contributor to atherosclerosis, cardiovascular diseases (CVD) [1, 2] and metabolic syndrome [3]
Endothelial microparticles as biomarker of endothelial activation can be exemplified by findings of microparticles captured with anti-CD62E+/E-selectin, anti-CD54+/ICAM-1, and anti-D106+/VCAM-1, whereas endothelial microparticles as biomarker of endothelial dysfunction is evidenced by findings of macroparticles captured with anti-annexin V to phosphatidylserine [9,10,11,12]
Many other molecules released from activated endothelium have been proposed as novel biomarkers of endothelial activation for atherosclerosis and other cardiometabolic diseases [9,10]

Summary

Introduction

Endothelial activation and dysfunction is an important contributor to atherosclerosis, cardiovascular diseases (CVD) (e.g., coronary artery disease, carotid artery disease, peripheral artery disease, and ischemic stroke) [1, 2] and metabolic syndrome [3]. Insulin resistance and endothelial dysfunction in these pathological disorders result in impairment in the nitric oxide - dependent vasodilatation, cellular glucose uptake, enhancement in oxidative stress, and inflammation All these lesions lead to atherosclerosis [4]. The linkage of activation biomarkers with dysfunction biomarkers can be exemplified in experiments of in vivo (APoE/LDLR double knockout mice) and in vitro (human aortic endothelial cells), in which cholesterol [hyperchoclesterolemia and 7-ketocholesterol (7K)] induced activation biomarkers (e.g., E-selectin, P-selectin, ICAM-1, VCAM-1), and induced a novel biomarker of endothelial dysfunction, endoglin [7] These findings suggest that activation biomarkers positively correlated with dysfunction biomarker in the face of potent systemic drivers of cardiovascular risk (e.g., hypercholesterolemia) [7]. Endothelial microparticles as biomarker of endothelial activation can be exemplified by findings of microparticles captured with anti-CD62E+/E-selectin, anti-CD54+/ICAM-1, and anti-D106+/VCAM-1, whereas endothelial microparticles as biomarker of endothelial dysfunction (e.g., endothelial apoptosis and damage) is evidenced by findings of macroparticles captured with anti-annexin V to phosphatidylserine [9,10,11,12]

Biomarkers of endothelial activation in cardiovascular diseases

Novel biomarkers of endothelial dysfunction in cardiovascular diseases

Discussion

Conclusions

Findings

Conflict of interest