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


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.


CONCLUSIONS
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.
Whittaker
Andrew
A
Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.
Moore
Jasbir S
JS
Vasa-Nicotera
Mariuca
M
Stevens
Suzanne
S
Samani
Nilesh J
NJ
D000328:Adult; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002452:Cell Count; D002465:Cell Movement; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006412:Hematopoietic Stem Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A