Abstract 022: Higher Baseline Progenitor Cell Counts in Familial Hypercholesterolemic Patients Compared to Healthy Controls

Abstract

Background: Endothelial injury from exposure to cardiovascular risk factors leads to atherosclerosis, however, an endogenous response to vascular injury characterized by circulating progenitor cells (CPCs) contributes to endothelial repair and regeneration. Although CPCs are known to be inversely related to cardiovascular risk, it is uncertain whether these risk factors are also a stimulus for CPC mobilization. We measured the number of CPCs in patients with familial hypercholesterolemia (FH) and compared them to patients with hyperlipidemia and healthy controls, with the hypothesis that CPC levels would be modulated by FH. Methods: Eight patients with FH on statin therapy (mean age, 48 ± 17 years) were compared with 16 age- and gender-matched hyperlipidemic patients on statin therapy, and 16 healthy volunteers. CPCs were analyzed using flow cytometry (BD FACS Canto II) for mononuclear cell (CD45dim) surface expression of CD34 and a combination of VEGF2R, CD133, and CXCR4 epitopes. Results are expressed as means ± SD or as proportions, and analysis of variance was used to detect differences between the three groups. Results: FH patients had higher circulating numbers of CD34+/CD133+ cells compared to hyperlipidemic (1.49 ± 1.01 vs. 0.88 ± 0.52 cells/µL, p = 0.04, respectively) and healthy counterparts (0.97 ± 0.61 cells/µL, p = 0.08). Similarly, FH subjects also had higher circulating levels of CD34+/CD133+/CXCR4+ cells compared to both the hyperlipidemic (0.68 ± 0.36 vs. 0.30 ± 0.22 cells/µL, p = 0.002, respectively) and healthy group (0.32 ± 0.25 cells/µL, p = 0.003). Conclusions: CPC counts, particularly of early CPCs characterized by CD133, and also those expressing the homing receptor, CXCR4, are higher in FH patients compared to age- and gender-matched healthy controls and patients with hyperlipidemia, independent of statins. This suggests an activation of reparative and regenerative reserve in FH subjects. The increased level of CPCs in FH subjects compared to hyperlipidemic patients may be a collective result of a higher level of lipid burden, lower therapeutic response to anti-hyperlipidemic pharmacotherapy, and chronic immune-activation due to ongoing subclinical endothelial injury in FH patients.