Analysis of endothelial progenitor subpopulation cells, oxidative DNA damage, and their role in coronary artery disease

Abstract

Background: Endothelial dysfunction has been associated for the cause of atherosclerosis or cardiovascular diseases (CVDs). Endothelial progenitor cells (EPCs) are exposed to oxidative stress during vascular injury as residents of blood vessel walls or as circulating cells homing to the sites of neovascularization. The current study was designed to analyze various subpopulations of EPCs and their DNA damage in CVDs. Methods: The study included 50 coronary artery disease (CAD) patients which was confirmed by angiography and 50 age-matched healthy controls without CAD. Flow cytometric analysis performed to measure subpopulations in EPCs in the peripheral blood using markers such as CD34, CD133, VEGFR2, and CD45. Oxidative DNA damage was analyzed in CD34+ cells. Mean EPC count was expressed as a percentage of total white blood cells. Three different subpopulations with CD45−/CD133+/VEGFR2+, CD45−/CD34+/VEGFR2+, and CD45−/CD34+/CD133+ coexpressions were measured with various percentages. Results: Subpopulation of CD45−/CD34+/VEGFR2+ cells had shown significant (P = 0.001) decrease in CAD patients in comparison with the healthy controls. There was no significant difference in the subpopulations of CD45−/CD34+/CD133+ cells (P = 0.005) and CD45−/CD133+/VEGFR2+ cells (P = 0.005) in CAD and healthy controls. The CD45−/CD34+/VEGFR2+ subpopulation EPC showed positive correlation with the severity of coronary stenosis (r = 0.35, P = 0.026), while other EPC subpopulation count did not show any correlation. Oxidative DNA damage was higher in CAD compared with controls. The number of EPC subpopulation CD45−/CD34+/VEGFR2+ was inversely correlated with oxidative DNA damage (P = 0.001), hypertension (P = 0.001), and diabetes mellitus (P = 0.004). Conclusion: We observed an association between CD45−/CD34+/VEGFR2 subpopulation EPCs and DNA damage in CAD condition. These findings support a cell biologist in searching the role of EPC populations in the pathophysiology or diagnosis of the disease by a clinician.