title: Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway.
abstract: Simvastatin (SIM) is a lipid-soluble inhibitor of hydroxy-3-methylglutaryl coenzyme A reductase with multiple reported therapeutic benefits. The present study was designed to investigate the effect of pretreatment with SIM on isoproterenol (ISO)-induced cardiac hypertrophy in rats. Twenty-four male albino Wistar rats weighing 180-200 g were divided into four groups. Groups I and III received normal saline while groups II and IV received SIM (10 mg/kg body weight) for 30 days per gavage. In the last 7 days, rats of groups III and IV were administered ISO (5 mg/kg) intraperitoneally to induce cardiac hypertrophy. Administration of ISO induced an increase in heart-to-body weight (HW/BW) ratio, an increase in serum interleukin-6, and elevated systolic and diastolic blood pressure. Serum levels of lipids, cardiovascular risk indices, and cardiac troponin I and creatine phosphokinase-MB showed significant increase in ISO-induced hypertrophic rats. Histopathological examination of heart tissue revealed focal areas of subendocardium degeneration, mononuclear cellular infiltrations, fibrous tissue deposition, and increased thickness of the myocardium of left ventricle. In addition, ISO-administered rats exhibited significant upregulation of cardiac Janus kinase, phosphorylated signal transducer and activator of transcription, and nuclear factor-kappa B. Pretreatment with SIM significantly prevented ISO-induced cardiac hypertrophy, alleviated the altered biochemical parameters, and improved the heart architecture. In conclusion, our study provides evidence that SIM prevented the development of cardiac hypertrophy via modulation of the Janus kinase/signal transducer and activator of transcription-signaling pathway in the heart of ISO-administered animals.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Nouf M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Maha M
authors.initials: MM
authors.lastname: Al-Oteibi
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Reem Z
authors.initials: RZ
authors.lastname: Al-Manee
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Al-Shareef
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Nawal M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Iman H
authors.initials: IH
authors.lastname: Hasan
authors.affiliation: Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Raeesa A
authors.initials: RA
authors.lastname: Mohamad
authors.affiliation: Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt.
authors.forename: Ayman M
authors.initials: AM
authors.lastname: Mahmoud
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D006332:Cardiomegaly / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D052279:Creatine Kinase, MB Form / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D005355:Fibrosis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D007545:Isoproterenol; D053612:Janus Kinases / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019821:Simvastatin / Q000494:pharmacology*; D019210:Troponin I / Q000097:blood
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D008055:Lipids; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D019210:Troponin I; D019821:Simvastatin; D053612:Janus Kinases; D052279:Creatine Kinase, MB Form; D007545:Isoproterenol
keywords: IL-6; JAK/STAT pathway; cardiac hypertrophy; isoproterenol; simvastatin