Evidence for genetic regulation of endothelial progenitor cells and their role as biological markers of atherosclerotic susceptibility

Abstract

Aims: Endothelial progenitor cells (EPCs) are found in the peripheral circulation and are capable of endothelial repair and neovascularization. EPC number and function are reduced in subjects with cardiovascular risk factors or proven coronary artery disease (CAD). We hypothesized that EPC number and/or function may be genetically regulated and may vary in healthy adult offspring depending on parental history of CAD.

Methods and results: We studied 102 subjects comprising 24 healthy parent-healthy offspring pairs and 27 CAD parent-healthy offspring pairs. We measured the number of circulating CD34(+)VEGFR-2(+) and AC133(+)VEGFR-2(+) EPCs, the number of EPCs grown in culture, and the migration capacity of cultured EPCs towards vascular endothelial growth factor. There was significant correlation in the number of cultured EPCs between healthy parents and their offspring (R = 0.492, P = 0.015) and CAD parents and their offspring (R = 0.751, P < 0.001). Offspring of subjects with CAD had significantly higher numbers of circulating CD34(+)VEGFR-2(+) and AC133(+)VEGFR-2(+) cells (P = 0.018 and P < 0.001, respectively). There was no difference in migration capacity between groups.

Conclusion: Our results suggest that EPC number is, at least in part, genetically regulated. Circulating EPCs may represent biological markers of occult vascular damage in offspring with hereditary risk of CAD.