Rad GTPase Attenuates Vascular Lesion Formation by Inhibition of Vascular Smooth Muscle Cell Migration
| Autor: | Taixing Cui, Yasuo Hamamori, Yan Xiao, C. Ronald Kahn, Yuqing E. Chen, Mingui Fu, Xiaojun Zhu, Hector De Leon, Yongshan Mou, Jifeng Zhang, Yu-Hua Tseng, Mary M.J. Chang |
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| Rok vydání: | 2005 |
| Předmět: |
Male
rho GTP-Binding Proteins Vascular smooth muscle medicine.medical_treatment Myocytes Smooth Muscle GTPase Protein Serine-Threonine Kinases Biology Muscle Smooth Vascular Rats Sprague-Dawley Neovascularization Restenosis Cell Movement Stress Fibers Physiology (medical) medicine Animals Humans Myocyte Aorta Focal Adhesions rho-Associated Kinases Neovascularization Pathologic Vascular disease Growth factor Intracellular Signaling Peptides and Proteins medicine.disease Actins Rats Cell biology Carotid Arteries Immunology ras Proteins Tumor necrosis factor alpha medicine.symptom Tunica Intima Cardiology and Cardiovascular Medicine Signal Transduction |
| Zdroj: | Circulation. 111:1071-1077 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.0000156439.55349.ad |
| Popis: | Background— Rad (Ras associated with diabetes) GTPase is a prototypic member of a new subfamily of Ras-related GTPases with unique structural features, although its physiological role remains largely unknown. In the present study, we characterized the Rad function in vascular smooth muscle cells (VSMCs) and the influence of adenovirus-mediated Rad (Ad-Rad) gene delivery on vascular remodeling after experimental angioplasty. Methods and Results— We documented for the first time that neointimal formation using balloon-injured rat carotid arteries was associated with a significant increase in Rad expression as determined by immunohistochemistry and quantitative real-time reverse-transcriptase polymerase chain reaction. The levels of Rad expression in VSMCs were highly induced by platelet-derived growth factor and tumor necrosis factor-α. Morphometric analyses 14 days after injury revealed significantly diminished neointimal formation in the Ad-Rad–treated carotid arteries compared with Ad-GFP or PBS controls, whereas the mutated form of Rad GTPase, which can bind GDP but not GTP, increased neointimal formation. Overexpression of Rad significantly inhibited the attachment and migration of VSMCs. In addition, Rad expression dramatically reduced the formation of focal contacts and stress fibers in VSMCs by blocking the Rho/ROK signaling pathway. Conclusions— Our data clearly identified Rad GTPase as a novel and critical mediator that inhibits vascular lesion formation. Manipulation of the Rad signaling pathway may provide new therapeutic approaches that will limit vascular pathological remodeling. |
| Databáze: | OpenAIRE |
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