title: Atorvastatin attenuates myocardial remodeling induced by chronic intermittent hypoxia in rats: partly involvement of TLR-4/MYD88 pathway.
abstract: Inflammatory processes and oxidative stress are known to play a key role in the development of cardiovascular complications such as cardiac hypertrophy induced by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological change of obstructive sleep apnea syndrome (OSAS). Current evidence suggests that competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA coenzyme A reductase, such as atorvastatin, not only reduce blood lipids but also have anti-inflammatory and inhibit oxidative stress benefits. This study examined the protective role of atorvastatin in CIH-induced cardiac hypertrophy. Adult male wistar rats were subjected to 8h of intermittent hypoxia/day, with/without atorvastatin for 6 weeks. Ventricular remodeling, toll-like receptor 4 (TLR-4), myeloid differentiation primary response protein 88 (MYD88), inflammatory agents and radical oxygen species were determined. As a result, we found that treatment with atorvastatin markedly inhibited the mRNA and protein expressions of TLR4, MYD88 and the downstream inflammatory agents and radical oxygen species. Administration of atorvastatin following CIH significantly ameliorated the myocardial injury, such as cardiac hypertrophy. In conclusion, Pre-CIH atorvastatin administration may attenuate TLR-4/MYD88 mediated inflammatory processes and oxidative stress in the injured rat myocardium, and this may be one mechanism by which atorvastatin ameliorated myocardial injury following CIH.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, China.
authors.forename: Die
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, China. Electronic address: hgliu@tjh.tjmu.edu.cn.
authors.forename: Huiguo
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D016207:Cytokines / Q000235:genetics; D006321:Heart / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000151:congenital / Q000503:physiopathology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
chemical_list: D016207:Cytokines; D006538:Heptanoic Acids; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D011758:Pyrroles; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D000069059:Atorvastatin
keywords: Atorvastatin; Cardiac hypertrophy; Chronic intermittent hypoxia; Inflammatory response; Toll-like receptor 4