RhoA and Rac1 Changes in the Atherosclerotic Lesions of WHHLMI Rabbits

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.

Positive Feedback Regulation of Proliferation in Vascular Smooth Muscle Cells Stimulated by Lipopolysaccharide Is Mediated through the TLR 4/Rac1/Akt Pathway

“…John reported that Rac1 participates in LPS activation of TLR4 expression [36]. In the carotid artery injury model, Ohkawara [37] reported that Rac1 activity is higher in atherosclerosis plaques, and is proportional to the degree of hardening of the arteries. Inhibition of Rac1 can inhibit VSMC proliferation induced by PDGF [38] and EGF [39].…”

Small G Proteins in the Cardiovascular System: Physiological and Pathological Aspects

“…B) RAC1. As RhoA, Rac1 expression and activity is increased in arteries from atherogenic animal models (196,255,351). Interestingly, Rac1 expression and activity are reduced by estrogen in vascular smooth muscle and monocytes, suggesting that this effect could participate in the atheroprotective action of estrogen (255).…”

“…RhoA expression and activity increase with cellular infiltration during the progression of atherosclerotic lesions (351). Downstream RhoA, Rho-kinases have been also shown to be upregulated at inflammatory arteriosclerotic lesions in both a porcine model of coronary artery spasm (211) and arteriosclerotic human arteries (212).…”

Rac1 modification by an electrophilic 15-deoxy Δ12,14-prostaglandin J2 analog

“…Rac1 is ubiquitously expressed in many cell types, and regulation is both dynamic and contextual. Previous studies have described Rac1 dysregulation as a contributing factor in an array of different pathologies including cardiovascular disease and cancer [1–4] . Dysregulation of Rac1 in endothelial cells (ECs) may be important in disease initiation and progression during cardiovascular disease.…”