title: Rad GTPase attenuates vascular lesion formation by inhibition of vascular smooth muscle cell migration.
abstract: 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.
  
  
  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-alpha. 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.
authors.affiliation: Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Ga 30310, USA.
authors.forename: Mingui
authors.initials: M
authors.lastname: Fu
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Tseng
authors.forename: Taixing
authors.initials: T
authors.lastname: Cui
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yongshan
authors.initials: Y
authors.lastname: Mou
authors.forename: Hector
authors.initials: H
authors.lastname: De Leon
authors.forename: Mary M J
authors.initials: MM
authors.lastname: Chang
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hamamori
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.forename: Yuqing E
authors.initials: YE
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology; D002339:Carotid Arteries; D002465:Cell Movement / Q000502:physiology*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D022502:Stress Fibers / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000096:biosynthesis / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D054460:rho-Associated Kinases
chemical_list: D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; C084355:RRAD protein, human; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D018631:ras Proteins; D020741:rho GTP-Binding Proteins