Abstract 18653: Decreased Levels of Circulating ‰Early Vascular Progenitor Cells are Associated with Cardiovascular Disease Risk

Abstract

Circulating levels of vascular progenitor cells (VPCs) have been suggested to be reflective of cardiovascular disease (CVD) risk. However, VPCs are a heterogeneous population containing cells with different angiogenic potential, and it is not clear which specific cell types are associated with CVD risk and specific CVD risk factors. We evaluated the relationship between CVD risk factors using antigenically-defined VPC sub-populations with or without validated angiogenic potential. Circulating VPC populations were measured in 240 high risk adults enrolled in the Louisville Healthy Heart Study. To quantify VPC levels, peripheral blood samples were stained with antigenic markers to define 6 different populations and analyzed using flow cytometry. CVD risk data were obtained from questionnaires, medical records, and blood/urine analyses. Generalized linear mixed-effects models were developed to examine the associations between mean VPC levels and the Framingham Risk Score (FRS) and CVD risk factors. A stepwise procedure was used to determine the most parsimonious model. The sample population was 54% male, 51±1 years old, 41% African-American, 39% current smokers, and had a mean FRS of 6±1. Levels of VPC subpopulations, VPC1 (CD31+/34+/45-), VPC3 (CD31+/34+/45-/AC133+), and VPC4 (CD31+/34+/45+/AC133+), significantly predicted FRS (β=-0.13 to -0.25; p=0.04 to 0.006) and showed stronger associations than previous reports using the entire VPC population. VPC2 (CD31+/34+/45+) and VPC6 (CD31+/34+) were not significantly associated with FRS. Moreover, VPC3 levels showed a strong positive association with circulating levels of platelet-leukocyte aggregates (CD41+/CD45+), whereas only the CD31+/AC133+ cells (VPC5) showed a negative association with LDL-C levels. None of the VPC sub-populations were correlated with serum fibrinogen or CRP levels. These observations indicate that immature (“early”) and non-monocytic (CD45-) VPCs levels are indicative of CVD risk and that the depletion of early VPCs (AC133+) may be reflective of a pro-thrombotic state and hypercholesterolemia but not systemic inflammation. Prospective longitudinal studies are required to assess the prognostic utility of measuring VPC subpopulations in peripheral blood.