RhoA and Rac1 changes in the atherosclerotic lesions of WHHLMI rabbits

J Atheroscler Thromb. 2009;16(6):846-56. doi: 10.5551/jat.2394. Epub 2009 Dec 22.

Abstract

Aim: The activation of RhoA and Rac1 is crucial for the pathogenesis of atherosclerosis. This study investigated the changes of unprocessed and mature forms of RhoA and Rac1 in the progression of atherosclerosis.

Methods: Unprocessed and geranylgeranylated forms of RhoA and Rac1 in aortic atherosclerotic lesions were separated by the Triton X-114 partition method using Watanabe heritable hyperlipidemic (WHHLMI) rabbits prone to myocardial infarction. The activation of RhoA and Rac1 was determined by membrane translocation and pull-down assays.

Results: The levels of unprocessed RhoA and Rac1 of the aortas were higher at 7 months than 3 months, accompanied by increased levels of total RhoA and Rac1. Membrane-bound RhoA and Rac1 levels of the aortas at 7 months were significantly increased compared with those at 3 months, consistent with the results of GTP-loading. Unprocessed and activated forms of RhoA and Rac1 had gradually decreas at 15 and 24 months compared to 7 months.

Conclusions: We show evidence of marked increases in unprocessed RhoA and Rac1 with enhanced activities in the progression of atherosclerosis in WHHLMI rabbits. This is important for better understanding of the pathogenesis of hyperlipidemia-dependent atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / metabolism*
  • Detergents / pharmacology
  • Disease Progression
  • Female
  • Gene Expression Regulation
  • Guanosine Triphosphate / metabolism
  • Hyperlipidemias / metabolism
  • Immunohistochemistry / methods
  • Male
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Octoxynol
  • Polyethylene Glycols / pharmacology
  • Rabbits
  • rac1 GTP-Binding Protein / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Detergents
  • Polyethylene Glycols
  • Guanosine Triphosphate
  • Octoxynol
  • Nonidet P-40
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein