S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Regulation of endothelial cell and endothelial progenitor cell survival and vasculogenesis by integrin-linked kinase
- Cho, Hyun-Jai; Youn, Seock-Won; Cheon, Soo-In; Kim, Tae-Youn; Hur, Jin; Zhang, Shu-Ying; Lee, Seung Pyo; Park, Kyung-Woo; Lee, Myoung-Mook; Choi, Yun-Shik; Park, Young-Bae; Kim, Hyo-Soo
- Issue Date
- American Heart Association
- Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1154-60. Epub 2005 Mar 31.
- Animals; Apoptosis/physiology; Cell Adhesion/physiology; Cell Division/physiology; Cell Survival/physiology; Cells, Cultured; Endothelium, Vascular/*cytology/*enzymology; Female; Gene Expression Regulation, Enzymologic; Gene Transfer Techniques; Humans; Ischemia/metabolism/pathology/physiopathology; Mice; Mice, Nude; Neovascularization, Physiologic/*physiology; Protein-Serine-Threonine Kinases/genetics/*metabolism; Signal Transduction/physiology; Stem Cells/*cytology/*enzymology; Umbilical Veins/cytology
- 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 3beta, 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.
- 1524-4636 (Electronic)