guanosine-triphosphate and Hyperlipidemias

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

The effect of prostaglandin E1 alpha-cyclodextrin host molecule (PGE1 . CD) was estimated by using a model of immune complex glomerulonephritis induced in rats by i.v. injection of 1 mg of rabbit serum albumin every other day. PGE1 . CD was given subcutaneously for 10 days after nephritis was definitely induced and resulted in a rapid restoration of various biochemical parameters, especially in plasma. The continuous s.c. administration of PGE1 . CD (300 micrograms/rat/day) with a mini osmotic pump provoked a therapeutic effect similar to that obtained with twice daily s.c. administration of PGE1 . CD (300 micrograms/rat X 2/day). Both PGE1 . CD groups revealed less glomerular damage and fewer locations of immune complexes in glomeruli as demonstrated by light and immunofluorescence microscopy. The beneficial effect of PGE1 . CD may be associated with reduced immune complex deposits in glomeruli. The present studies suggest that PGE1 . CD may enhance the clearance of immune complex deposits from the glomeruli rather than inhibiting the formation of immune complex in the circulation.

Topics: Acetylglucosaminidase; Alkaline Phosphatase; alpha-Cyclodextrins; Alprostadil; Animals; Body Weight; Cyclodextrins; Dextrins; Fluorescent Antibody Technique; Guanosine Triphosphate; Hyperlipidemias; Immune Complex Diseases; Kidney Glomerulus; Male; Nephritis; Prostaglandins E; Proteinuria; Rats; Rats, Inbred Strains; Starch; Time Factors; Uremia