Abstract 20539: Reduced Endothelial Progenitor Cells (EPCs) in Patients with Severe Hypertension
Background: Hypertensive crisis and severe uncontrolled hypertension are associated with progressive or life-threatening target organ damage_a process mediated by endothelial dysfunction and vascular injury. Bone marrow-derived, circulating endothelial progenitor cells (EPCs) contribute to vascular regeneration and repair, thereby protecting against hypertensive vasculopathy. The Aim of this study was to determine whether reduced EPC levels, and/or induction of EPC senescence with subsequent impaired self-renewal accounted for the decreased vascular repair capability in patients with severe uncontrolled hypertension.
Methods: Circulating EPC levels were quantified in 10 patients with severe hypertension and 10 matching healthy controls by colony forming unit (CFU) assay in vitro, and flow cytometry using CD34, CD133 and vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) antibodies. Cell senescence was determined by the expression of senescence-associated β-galactosidase (SA-β-Gal) and cell cycle arrest protein p16ink .
Results: In vitro, CFU assay revealed markedly decreased EPC levels in severe hypertension patients relative to healthy subjects (11.6±3.2 1 vs. 27.1±4, p=0.009). The number of CD34+/CD133+ and CD133+/VEGFR2+ EPCs were lower in patients with severe hypertension (4.2±1.2 vs. 15.5±4.6, p=0.036; 4.6±1.3 vs. 15.2±1.8, p=0.0003, respectively) compared with controls. The level of CD34+/VEGFR-2+ cells was no different between these two groups. Remarkably, SA-β-Gal-positive EPCs in hypertension was substantially increased, senescence-associated p16ink4a expression was 3.9 fold greater in EPCs derived from hypertensive patients compared with those from healthy controls.
Conclusions: Patients with severe hypertension have lower levels of circulating EPCs, and increased senescence-associated p16ink4a expression in EPCs may account, at least in part, for the decreased circulating EPC levels in severe hypertension patients. Rejuvenation of EPCs may represent an important approach to improve the functional activity of EPCs and to reduce the mortalities and morbidities associated with hypertensive crisis.
- © 2010 by American Heart Association, Inc.