Abstract 13763: Circulating Endothelial Progenitor Cell Phenotypes are Weakly Associated With Select Biomarkers of Inflammation
Introduction: Depletion of circulating endothelial progenitor cell phenotypes, conventionally termed ‘EPCs’, has been associated with higher cardiovascular disease (CVD) risk. Although systemic inflammation also has been associated with CVD risk, the extent to which markers of inflammation are associated with EPCs is unknown.
Methods: We evaluated 1,717 participants of the Framingham Offspring Study (mean age 66±9 years, 53% women) during the 7th exam cycle (1998-2001). Cell phenotyping was performed using an early-outgrowth colony-forming unit assay and cell surface markers (CD34 and KDR). We also assayed biomarkers representing 10 distinct inflammatory pathways: CRP, ICAM-1, IL-6, isoprostanes, LpPLA2 activity and mass, MCP-1, osteoprotegerin, P-selectin, and TNF receptor II. We constructed regression models to assess relations of inflammatory biomarkers to EPCs, adjusting for traditional risk factors (age, sex, smoking status, systolic blood pressure, diastolic blood pressure, body mass index, total cholesterol/HDL, LDL, triglycerides, glucose, diabetes, aspirin use, antihypertensive therapy, hormone replacement therapy, and prevalent CVD). A Bonferroni-corrected threshold of P<0.001 was used to account for multiple testing.
Results: In age- and sex-adjusted analyses, ICAM-1 (β 0.58±0.01, P=0.0001) and osteoprotegerin (β -0.05±0.01, P=0.0004) were associated with CD34+. These associations remained statistically significant in multivariable-adjusted analyses: β 0.18±0.04 (P=0.0001) and β -0.14±0.05 (P=0.002), respectively. The other biomarkers tested were not significantly associated with any EPC phenotypes.
Conclusion: In this large, community-based study we observed a weakly positive association of CD34+ cells with ICAM-1 (a marker of inflammation) and weak negative association with osteoprotegerin (a marker of vascular calcification). These results could reflect augmentation of progenitors as part of a compensatory response to inflammatory exposures, and depletion of progenitors in the setting of calcific vascular disease. Further research is needed to clarify the biological interplay between inflammatory and vasculogenic pathways.
- © 2011 by American Heart Association, Inc.