Certain Manipulation Strategies For Angiogenesis Process Associated With Atherosclerosis in Cholesterol Fed Rabbit

The aim of the present work involves the effectiveness of a specific inhibitor of c.AMP phosphodiesterase (Cilostazol), a ligand for peroxisome proliferative activated receptor (PPAR)- (Fenofibrate)anda precursor of reduced glutathione (GSH) antioxidant (N-acetylcysteine) in reducing atherosclerosis progression induced by hyperlipidemia in experimental rabbits. This is done through long term supplementation of diet enriched with cholesterol, cholic acid and corn oil. The studied parameters were: 1-In serum: {LDH, CK and lipid profile (TC, TG, LDL, and HDL)} 2-In aorta tissue: {VEGF, MMP-3, eNOS, iNOS, NFB, HO-1, superoxide anion, MDA and Ca++ ion} 3-Histopathological examinations of aorta tissue isolated from experimental rabbits to configure the effects of selected drugs on these tissue and investigate their possible correlation with the biochemical results. Experimental design: Rabbits were randomly divided into 5 groups among them normal diet group fed on rabbit chow (n=6) without any additives and other 4 groups kept on hypercholesterolemic diet for 6 weeks. Hypercholesterolemic diet consisted of rabbit chow enriched with 1% (w/w) cholesterol, 0.5% cholic acid and 6% (w/w) corn oil and received plain tap water ad libitum. Blood samples were directed for cholesterol determination. Selection of animals that have serum cholesterol level above 250 mg/dl. Subsequently, they were categorized as follow: Group (1): Control rabbits fed on hypercholesterolemic diet (n=6). Group (2): Hypercholesterolemic rabbits were orally received cilostazol (25 mg/kg) for 6 weeks (n=6). Group (3): Hypercholesterolemic rabbits were orally received fenofibrate (30 mg/kg) for 6 weeks (n=6). Group (4): Hypercholesterolemic rabbits were orally received N-acetylcysteine (150 mg/kg) for 6 weeks (n=6).