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

• Published in: Atherosclerosis 2007-05, Vol.192 (1), p.92-99
• Main Authors: Noor, Raza, Shuaib, Umar, Wang, Chen Xu, Todd, Kathryn, Ghani, Usman, Schwindt, Brenda, Shuaib, Ashfaq
• Format: Article
• Language: English
• Subjects: Aged; Apoptosis - physiology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation. Blood cells; Blood vessels and receptors; Cardiology. Vascular system; Cardiovascular; Caspase 3 - metabolism; Cell Culture Techniques; Cholesterol; Cholesterol, HDL - blood; Cholesterol, HDL - physiology; Endothelial Cells - cytology; Endothelial Cells - enzymology; EPC; Female; Fundamental and applied biological sciences. Psychology; HDL; Humans; Male; Medical sciences; Middle Aged; Molecular and cellular biology; Nitric Oxide Synthase Type III - metabolism; Platelet; Serine Endopeptidases - metabolism; Stem Cells - metabolism; Stroke; Vascular; Vertebrates: cardiovascular system
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2006.06.023

Abstract 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.