title: Augmentation of autophagy by atorvastatin via Akt/mTOR pathway in spontaneously hypertensive rats.
abstract: Autophagy is activated in hypertension-induced cardiac hypertrophy. However, the mechanisms and significance of an activated autophagy are not clear. This study was designed to determine the role of atorvastatin (ATO) in cardiac autophagy and associated benefits on cardiac remodeling and left ventricular function in spontaneously hypertensive rats (SHRs). Twenty-eight male SHRs at 8 weeks of age were randomized to treatment with vehicle (saline solution; SHR+V) or ATO (SHR+ATO; 50 mg kg(-1) per day) for 6 or 12 months. Age-matched male Wistar-Kyoto (WKY) rats were used as normotensive controls. Cardiac magnetic resonance was used to evaluate cardiac function and structure. Compared with WKY rats, SHRs showed significant left ventricle (LV) dysfunction, remodeling and increases in cardiomyocyte size, which were all attenuated by 6 and 12 months of ATO treatment. Compared with WKY rats, autophagy was activated in the hearts of SHRs and this effect was amplified by chronic ATO treatment, particularly following 12 months of treatment. Protein expression levels of microtubule-associated protein-1 light chain 3-II and beclin-1, the biomarkers of an activated cardiac autophagy, were significantly elevated in ATO-treated versus vehicle-treated SHRs and control WKY rats. Cardiac Akt and phosphorylated mammalian target of rapamycin (mTOR) expression were also increased in the hearts of SHR versus WKY rats, and this effect was attenuated by ATO treatment. These findings suggest that ATO-mediated improvements in LV function and structure in SHRs may be, in part, through its regulation of cardiac autophagy via the Akt/mTOR pathway.
authors.affiliation: Department of Cardiovascular Surgery, Shandong University Qilu Hospital, Shandong, China.|Department of Cardiology, Shandong Provincial Chest Hospital, Shandong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, Shandong, China.
authors.forename: Qing-Xin
authors.initials: QX
authors.lastname: Geng
authors.affiliation: Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, Shandong, China.
authors.forename: Hua-Ting
authors.initials: HT
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, Shandong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Miao
authors.affiliation: Department of Cardiology, Shandong Provincial Chest Hospital, Shandong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Shandong University of Traditional Chinese Medicine, Shandong, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular Surgery, Shandong University Qilu Hospital, Shandong, China.
authors.forename: Guang-Min
authors.initials: GM
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Groban
authors.initials: G
authors.lastname: Leanne
authors.affiliation: Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, Shandong, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases