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 mu g/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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.