Abstract 13457: Ldl-Induced Changes in Monocyte Populations and Ccr2 Expression Profile as a Potential Contributor to Cvd Risk in African Americans

Background:Cardiovascular disease (CVD) disproportionately affects minority populations; biologic mechanisms that promote higher CVD risk are understudied in diverse populations. We have previously shown that vascular inflammation correlates positively with total monocyte counts from clinical blood counts (CBC) in a community-based cohort of 42 African Americans (AA). CBC could not differentiate between monocyte subsets?information we thought to be of importance. Therefore, we took an ex vivoapproach.Methods and Results:PBMCs from a healthy blood bank donor were isolated and treated with 10% participant serum overnight followed by flow cytometry analysis of monocyte subsets and their chemokine receptor 2&5 expression (CCR2/CCR5). Linear regression analysis revealed that classical monocytes displayed a negative correlation with LDL levels (?=-0.38, p=0.02). Non-classical and intermediate monocytes displayed a positive correlation with LDL (?=0.38, p=0.02; ?=0.36, p=0.03, respectively). The expression of CCR2 on non-classical monocytes significantly correlated with total cholesterol levels (?=0.37, p=0.03) while a trend with LDL levels was observed (?=0.31, p=0.06). This prompted us to investigate LDL?s role in CCR2/5 expression in vitro. PBMC?s from five healthy blood bank donors were treated with LDL for 4h. We observed that LDL induced a significant decrease in classical monocytes while non-classical, pro-inflammatory monocytes doubled (Figure). A 20% increase in CCR2 expression was detected upon LDL treatment only in non-classical monocytes.Conclusions:Our data suggest that LDL initiates trans-differentiation of monocytes towards a pro-inflammatory phenotype while simultaneously increasing chemokine receptor CCR2 expression in an AA population. Larger studies are needed to examine potential mechanisms that promote these CCR2 expression changes and may be associated with increased CVD risk among African Americans.