title: Atorvastatin prevents left ventricular remodeling in spontaneously hypertensive rats.
abstract: Statins improve left ventricular (LV) remodeling in spontaneously hypertensive rats (SHRs). This study was designed to investigate the effects of atorvastatin administered in the early stage on LV remodeling in SHRs, and to explore the underlying mechanisms.Sixteen male 8-week-old SHRs were randomized to receive distilled water (SHR-DW) or atorvastatin (SHR-ATV) for 12 weeks. Age-matched male Wistar-Kyoto (WKY) rats gavaged with distilled water served as controls. LV remodeling was evaluated, myocardial CTGF expression levels were detected using Western blotting, and cardiomyocyte apoptosis was detected with the TUNEL method.Compared with WKY and SHR-DW, atorvastatin treatment significantly decreased systolic blood pressure in SHRs; atorvastatin significantly inhibited LV remodeling, as indicated by the reduced LV weight/body weight ratio (SHR-ATV: 4.0 ± 0.4 versus SHR-DW: 4.7 ± 0.4 mg/g, P < 0.05), cardiomyocyte diameter (SHR-ATV: 16.2 ± 2.8 versus SHR-DW: 19.0 ± 1.0 µm, P < 0.05), and interstitial fibrosis (SHR-ATV: 3.3 ± 2.1 versus SHR-DW: 4.5 ± 1.8%, P < 0.05). Compared with WKY, myocardial CTGF expression was significantly increased and cardiomyocyte apoptosis decreased in SHRs. Compared with the SHR-DW group, atorvastatin treatment significantly inhibited myocardial CTGF expression (SHR-ATV: 0.69 ± 0.21 versus SHR-DW: 1.12 ± 0.27, P < 0.05) and induced cardiomyocyte apoptosis in SHRs (SHR-ATV: 5.2 ± 0.6 versus SHR-DW: 1.9 ± 0.3%, P < 0.05).The results indicate that early-stage administration of atorvastatin effectively prevented LV remodeling in SHRs, and that inhibition of myocardial CTGF expression and induction of cardiomyocyte apoptosis may be the underlying mechanisms.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Zhengzhou University, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhao
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Jin-Ying
authors.initials: JY
authors.lastname: Zhang
authors.forename: Gang-Qiong
authors.initials: GQ
authors.lastname: Liu
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Chen
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Yang
authors.forename: Rui-Yun
authors.initials: RY
authors.lastname: Liu
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: C526316:CCN2 protein, rat; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D055513:Connective Tissue Growth Factor; D000069059:Atorvastatin