RhoA and Rac1 changes in the atherosclerotic lesions of WHHLMI rabbits.
OBJECTIVE
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.
Ohkawara
Hiroshi
H
Department of Cardiology and Hematology, Fukushima Medical University, Japan.
Ishibashi
Toshiyuki
T
Shiomi
Masashi
M
Sugimoto
Koichi
K
Uekita
Hironori
H
Kamioka
Masashi
M
Takuwa
Yoh
Y
Teramoto
Tamio
T
Maruyama
Yukio
Y
Takeishi
Yasuchika
Y
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006160:Guanosine Triphosphate / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D011817:Rabbits; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D003902:Detergents; D011092:Polyethylene Glycols; D006160:Guanosine Triphosphate; D017830:Octoxynol; C010615:Nonidet P-40; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein