guanosine-triphosphate and Atherosclerosis

The apolipoprotein A-I mimetic peptide D-4F, among its anti-atherosclerotic effects, improves vasodilation through mechanisms not fully elucidated yet.. Low-density lipoprotein (LDL) receptor null (LDLr. Unexpectedly, eNOS phosphorylation, eNOS-HSP90 association, and O. Hypercholesterolemia enhanced uncoupled eNOS activity by decreasing GCH-1 concentration, thereby reducing BH4 levels. D-4F reduced uncoupled eNOS activity by increasing BH4 levels through GCH-1 expression and decreasing eNOS phosphorylation and eNOS-HSP90 association. Our findings elucidate a novel mechanism by which hypercholesterolemia induces atherosclerosis and D-4F inhibits it, providing a potential therapeutic approach.

Topics: Animals; Apolipoprotein A-I; Atherosclerosis; Biopterins; Endothelial Cells; Endothelium, Vascular; GTP Cyclohydrolase; Guanosine Triphosphate; Mice; Nitric Oxide; Nitric Oxide Synthase Type III; Peptides; Superoxides

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.. 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.. 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.. 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.

Topics: Animals; Atherosclerosis; Detergents; Disease Progression; Female; Gene Expression Regulation; Guanosine Triphosphate; Hyperlipidemias; Immunohistochemistry; Male; Myocardial Infarction; Octoxynol; Polyethylene Glycols; Rabbits; rac1 GTP-Binding Protein; rhoA GTP-Binding Protein