Open AccessThe therapeutic effect of Rosuvastatin on cardiac remodelling from hypertrophy to fibrosis during the end‐stage hypertension in rats
Author(s) -
Zhang W.B.,
Du Q.J.,
Li H.,
Sun A.J.,
Qiu Z.H.,
Wu C.N.,
Zhao G.,
Gong H.,
Hu K.,
Zou Y.Z.,
Ge J.B.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01536.x
Subject(s) - rosuvastatin , medicine , fibrosis , endocrinology , muscle hypertrophy , cardiac fibrosis , hypertensive heart disease , heart failure
End‐stage hypertensive heart disease is an increasing cause of cardiac mortality. Therefore, the current study focused on the cardiac remodelling from hypertrophy to fibrosis in old‐aged spontaneously hypertensive rats ( SHRs ), and explored the therapeutic effects of Rosuvastatin and its possible mechanism(s) of action. Spontaneously hypertensive rats at age 52 weeks were randomly divided into three groups, the first two to receive Rosuvastatin at a dose of 20 mg/kg/day and 40 mg/kg/day, respectively, and the third to receive placebo, which was to be compared with Wistar‐Kyoto as controls. After 2‐month treatment, SBP , heart to body weight ratio ( HW/BW %) and echocardiographic features were evaluated, followed by haematoxylin and eosin and Masson trichrome staining in conjunction with qPCR of foetal gene expressions. Transferase‐mediated dUTP nick‐end labelling assay and immunofluorescent labelling for active caspase‐3 were used to detect the apoptotic cardiomyocytes. Signaling pathways involved were examined by using western blot. Old‐aged SHR developed end‐stage hypertensive heart disease characterized by significant enhancement of HW / BW %, LVAW d and LVPW d, and decreased LVEF and LVFS , accompanied by cardiomyocytes enlargement and fibrosis along with activation of foetal gene programme. Cardiac apoptosis increased significantly during the transition process. Rosuvastatin reduced hypertrophy significantly via AT 1 Receptor‐ PKC β2/α‐ ERK ‐c‐fos pathway; protected myocardium against apoptosis via A kt‐ FOXO 1, B cl‐2 family and survivin pathways and consequently suppressed the caspase‐3 activity. The present study revealed that old‐aged SHRs developed cardiac remodelling from hypertrophy to fibrosis via cardiac apoptosis during the end stage of hypertensive heart disease. These pathological changes might be the consequence of activation of AT 1 Receptor‐ PKC β2/α‐ ERK ‐c‐fos and AKT ‐ FOXO 1/ B cl‐2/survivin/Caspase3 signaling. Rosuvastatin effectively attenuated the structural changes by reversing the signaling transductions involved.