Published online before print March 31, 2005, doi: 10.1161/01.ATV.0000164312.20008.93
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© 2005 American Heart Association, Inc.
Vascular Biology |
Regulation of Endothelial Cell and Endothelial Progenitor Cell Survival and Vasculogenesis by Integrin-Linked Kinase
From the Department of Internal Medicine (H.-J.C., S.P.L., K.-W.P., M.-M.L., Y.-S.C., Y.-B.P., H.-S.K.), Seoul National University College of Medicine, Korea; Cardiovascular Center (H.-J.C., S.P.L., K.-W.P., M.-M.L., Y.-S.C., Y.-B.P., H.-S.K.), Seoul National University Hospital, Korea; and Cardiovascular Research Laboratory (H.-J.C., S.-W.Y., S.-I.C., T.-Y.K., J.H., S.-Y.Z., S.P.L., K.-W.P., M.-M.L., Y.-S.C., Y.-B.P., H.-S.K.), Clinical Research Institute, Seoul National University Hospital, Korea.
Correspondence to Hyo-Soo Kim, MD, PhD, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Korea. E-mail hyosoo{at}snu.ac.kr
Objective— New vessel formation is a dynamic process of attachment, detachment, and reattachment of endothelial cells (ECs) and endothelial progenitor cells (EPCs) with each other and with the extracellular matrix (ECM). Integrin-linked kinase (ILK) plays a pivotal role in ECM-mediated signaling. Therefore, we investigated the role of ILK in ECs and EPCs during neovascularization.
Methods and Results— In human umbilical cord vein ECs and EPCs, endogenous ILK expression, along with subsequent cell survival signals phospho-Akt and phospho–glycogen synthase kinase 3ß, was reduced after anchorage or nutrient deprivation. Even brief anchorage deprivation resulted in retarded capillary tube formation by ECs. Adenoviral ILK gene transfer in ECs and EPCs reversed the decrease in cell survival signals after anchorage or nutrient deprivation, leading to enhanced survival, reduced apoptosis, and significantly accelerated the functional recovery after reattachment. And ILK overexpressing EPCs significantly improved blood flow recovery and prevented limb loss in nude mice hindlimb ischemia model. Furthermore, the efficacy of systemic delivery was equivalent to local injection of ILK-EPCs.
Conclusions— ILK overexpression protects ECs and EPCs from anchorage- or nutrient-deprived stress and enhances neovascularization, suggesting that ILK is an optimal target gene for genetically modified cell-based therapy. Neovascularization is a dynamic process of detachment and reattachment of ECs and EPCs. Endogenous ILK expression was decreased in various stress conditions, and the gene transfer of ILK protected ECs and EPCs from temporary anchorage or nutrient deprivation. Furthermore, ILK gene transfer in EPCs significantly enhanced neovascularization in vivo.
Neovascularization is a dynamic process of detachment and reattachment of ECs and EPCs. Endogenous integrin-linked kinase (ILK) expression was decreased in various stress conditions, and the gene transfer of ILK protected ECs and EPCs from temporary anchorage or nutrient deprivation. Futhermore, ILK gene transfer in EPCs significantly enhanced neovascularization in vivo.
Key Words: angiogenesis • endothelium • ischemia • Integrin-linked kinase
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