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Objective: We investigated whether chronic in vivo administration of rosiglitazone improves atherosclerosis and vascular function and structure in heterozygous methylenetetrahydrofolate reductase (Mthfr) knockout mice (k/o), a model of mild hyperhomocysteinemia.

Methods: Wild-type (+/+) and heterozygous (+/−) Mthfr k/o mice, age 12–13 months, were studied. Mthfr+/− were fed or not a hypercholesterolaemic diet (20 g/kg/day, HD) and treated or not with rosiglitazone (20 mg/Kg/day). Functional and mechanical studies were performed on a myograph on segments of pressurized (60 mmHg) internal carotid arteries. Endothelium-dependent relaxation was assessed with acetylcholine (Ach, 10− 9− 10− 4 M)±the nitric oxide synthase (NOS) inhibitor LNAME (10− 4 M). Endothelium-independent relaxation was assessed with sodium nitroprusside (SNP, 10− 8− 10− 3 M). Endothelial NOS (eNOS) activation was …