High-density lipoprotein cholesterol regulates endothelial progenitor cells by increasing eNOS and preventing apoptosis

Objective Endothelial progenitor cells (EPCs) are implicated as an important marker of endothelial function and cardiovascular risk. In the present study, we examined whether high-density lipoprotein (HDL) cholesterol plays a role in the peripheral EPC levels and its underlying mechanisms in the HDL cholesterol-induced elevation of EPCs. Methods For the clinical study, vascular risk factors and blood markers were measured and EPC colony forming units were counted after 7 days of culture. For the in vitro study, after 7 days of culture, EPCs were incubated in the presence or absence of HDL for 24 h followed by measurements of eNOS and pro-MMP-9 expression and caspase-3 activity. Results EPC colony levels significantly correlated with HDL levels (P = 0.017). HDL treatment significantly increased eNOS protein expression in EPCs (P < 0.001) while it significantly decreased pro-MMP-9 levels at the concentration of 50 μg/mL (P = 0.002). Homocysteine treatment significantly increased caspase-3 activity whereas HDL significantly decreased it as compared to the homocysteine-only treated group. Interpretation The data demonstrate that EPC colony levels are significantly lower in individuals with low HDL and that HDL increases eNOS and decreases pro-MMP-9 in EPCs. HDL also prevents EPC apoptosis through inhibition of caspase-3 activity suggesting a possible mechanism for its positive effects on circulating EPC numbers.