Angiotensin II Impairs Endothelial Progenitor Cell Number and Function In Vitro and In Vivo

作者：Cathleen Endtmann, Talin Ebrahimian, Thomas Czech, Omar Arfa, Ulrich Laufs, Mathias Fritz, Kerstin Wassmann, Nikos Werner, Vasileios Petoumenos, Georg Nickenig, Sven Waßmann · 发表于：Hypertension · 年份：2011 · DOI：10.1161/hypertensionaha.110.169193 · 被引用次数：95 · 研究领域：Angiogenesis and VEGF in Cancer、Zebrafish Biomedical Research Applications、Congenital heart defects research

Endothelial progenitor cells (EPCs) contribute to endothelial regeneration. Angiotensin II (Ang II) through Ang II type 1 receptor (AT(1)-R) activation plays an important role in vascular damage. The effect of Ang II on EPCs and the involved molecular mechanisms are incompletely understood. Stimulation with Ang II decreased the number of cultured human early outgrowth EPCs, which express both AT(1)-R and Ang II type 2 receptor, mediated through AT(1)-R activation and induction of oxidative stress. Ang II redox-dependently induced EPC apoptosis through increased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase phosphorylation; decreased Bcl-2 and increased Bax expression; and activation of caspase 3 but had no effect on the low cell proliferation. In addition, Ang II impaired colony-forming and migratory capacities of early outgrowth EPCs. Ang II infusion diminished numbers and functional capacities of EPCs in wild-type (WT) but not AT(1)a-R knockout mice (AT(1)a(-/-)). Reendothelialization after focal carotid endothelial injury was decreased during Ang II infusion. Salvage of reendothelialization by intravenous application of spleen-derived progenitor cells into Ang II-treated WT mice was pronounced with AT(1)a(-/-) cells compared with WT cells, and transfusion of Ang II-pretreated WT cells into WT mice without Ang II infusion was associated with less reendothelialization. Transplantation of AT(1)a(-/-) bone marrow reduce...