Atorvastatin attenuates myocardial remodeling induced by chronic intermittent hypoxia in rats: Partly involvement of TLR-4/MYD88 pathway

• Published in: Biochemical and biophysical research communications 2014-03, Vol.446 (1), p.292-297
• Main Authors: Yuan, Xiao, Deng, Yan, Guo, Xueling, Shang, Jin, Zhu, Die, Liu, Huiguo
• Format: Article
• Language: English
• Subjects: Animals; Atorvastatin; Atorvastatin Calcium; Cardiac hypertrophy; Cardiomegaly - etiology; Cardiomegaly - metabolism; Cardiomegaly - prevention & control; Chronic intermittent hypoxia; Cytokines - genetics; Heart - drug effects; Heptanoic Acids - pharmacology; Hypoxia - complications; Hypoxia - physiopathology; Inflammatory response; Male; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Myocardium - metabolism; Myocardium - pathology; Oxidative Stress - drug effects; Pyrroles - pharmacology; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Sleep Apnea, Obstructive - congenital; Sleep Apnea, Obstructive - physiopathology; Toll-like receptor 4; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Ventricular Remodeling - drug effects; Ventricular Remodeling - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.02.091

•Chronic intermittent hypoxia (CIH) leads to cardiac hypertrophy in rats.•Inflammatory processes and oxidative stress are highly induced by CIH in myocardial tissue.•Atorvastatin attenuates CIH-induced cardiac hypertrophy in rats by suppressing inflammatory processes and oxidative stress.•Attenuation of CIH-induced cardiac hypertrophy by atorvastatin may be mediated through the TLR-4/MYD88 signaling pathway. 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 6weeks. 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.