Genetic and clinical correlates of early-outgrowth colony-forming units

Stanley Y. Shaw, Susan Cheng, L. Adrienne Cupples, Martin G. Larson, Elizabeth L. McCabe, Julius S. Ngwa, Ying A. Wang, Roderick P. Martin, Rachael J. Klein, Basma Hashmi, Olujimi A. Ajijola, Evan Lau, Christopher J. O'Donnell, Ramachandran S. Vasan, Kenneth S. Cohen, Thomas J. Wang

Resultado de la investigación: Articlerevisión exhaustiva

14 Citas (Scopus)


Background-Several bone marrow-derived cell populations may have angiogenic activity, including cells termed endothelial progenitor cells. Decreased numbers of circulating angiogenic cell populations have been associated with increased cardiovascular risk. However, few data exist from large, unselected samples, and the genetic determinants of these traits are unclear. Methods and Results-We examined the clinical and genetic correlates of early-outgrowth colony-forming units (CFUs) in 1799 participants of the Framingham Heart Study (mean age, 66 years; 54% women). Among individuals without cardiovascular disease (n=1612), CFU number was inversely related to advanced age (P=0.004), female sex (P=0.04), and triglycerides (P=0.008) and positively related to hormone replacement (P=0.008) and statin therapy (P=0.027) in stepwise multivariable analyses. Overall, CFU number was inversely related to the Framingham risk score (P=0.01) but not with prevalent cardiovascular disease. In genome-wide association analyses in the entire sample, polymorphisms were associated with CFUs at the MOSC1 locus (P=3.3×10 -7) and at the SLC22A3-LPAL2-LPA locus (P=4.9×10 -7), a previously replicated susceptibility locus for myocardial infarction. Furthermore, alleles at the SLC22A3-LPAL2-LPA locus that were associated with decreased CFUs were also related to increased risk of myocardial infarction (P=1.1×10 -4). Conclusions-In a community-based sample, early-outgrowth CFUs are inversely associated with select cardiovascular risk factors. Furthermore, genetic variants at the SLC22A3-LPAL2-LPA locus are associated with both decreased CFUs and an increased risk of myocardial infarction. These findings are consistent with the hypothesis that decreased circulating angiogenic cell populations promote susceptibility to myocardial infarction.

Idioma originalEnglish (US)
Páginas (desde-hasta)296-304
Número de páginas9
PublicaciónCirculation: Cardiovascular Genetics
EstadoPublished - jun 2011
Publicado de forma externa

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)
  • Genetics


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