title: Atorvastatin modulates the DDAH1/ADMA system in high-fat diet-induced insulin-resistant rats with endothelial dysfunction.
abstract: Dimethylarginine dimethyl-aminohydrolase 1 (DDAH1) is a metabolic enzyme for asymmetric dimethylarginine (ADMA), both of which are closely related to endothelial function. Endothelial dysfunction, a main risk factor of cardiovascular diseases, can be attributed to insulin resistance. We aimed to determine the effects of atorvastatin, an endothelium-protective drug, on DDAH1/ADMA in insulin-resistant rats. Insulin resistance in male Sprague-Dawley rats was induced with a high-fat diet for 8 weeks. Some rats received atorvastatin (30 mg/kg/day) for an additional 8 weeks. Insulin-resistant rats exhibited not only decreases in the DDAH activity and aortic expression of DDAH1 and sterol regulatory element-binding protein 1 (SREBP1) but also increases in plasma ADMA levels, all of which were inhibited by atorvastatin. Insulin sensitivity and DDAH activity showed a significant positive correlation. In conclusion, our results suggest that atorvastatin may modulate DDAH1/ADMA to improve endothelial function in insulin-resistant rats; SREBP1 may also play a role in this.
authors.affiliation: Cardiology Department, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Po
authors.initials: P
authors.lastname: Chen
authors.forename: Ke
authors.initials: K
authors.lastname: Xia
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhao
authors.forename: Xu
authors.initials: X
authors.lastname: Deng
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D000069059:Atorvastatin; D059305:Diet, High-Fat; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006538:Heptanoic Acids; D007328:Insulin; D011758:Pyrroles; C487735:dimethylarginine; D001120:Arginine; D000069059:Atorvastatin; D000581:Amidohydrolases; C059999:dimethylargininase