The therapeutic effect of Rosuvastatin on cardiac remodelling from hypertrophy to fibrosis during the end-stage hypertension in rats
Autor: | Hao Li, Guochao Zhao, Kai Hu, Yunzeng Zou, Hui Gong, Junbo Ge, Wenbin Zhang, Chaoneng Wu, Qijun Du, Aijun Sun, Zhaohui Qiu |
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Rok vydání: | 2012 |
Předmět: |
Male
medicine.medical_specialty Survivin Apoptosis Nerve Tissue Proteins Biology Rats Inbred WKY Muscle hypertrophy Rosuvastatin Fibrosis Rats Inbred SHR Internal medicine Protein Kinase C beta medicine Animals Myocytes Cardiac Rosuvastatin Calcium Ventricular remodeling Protein Kinase C Sulfonamides old-aged spontaneously hypertensive rats Receptors Angiotensin Angiotensin II receptor type 1 Ejection fraction Ventricular Remodeling Caspase 3 fibrosis cardiac remodelling Forkhead Transcription Factors Hypertrophy Original Articles Cell Biology medicine.disease Hypertensive heart disease Rats Fluorobenzenes 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA)-reductase inhibitors Pyrimidines Endocrinology Hypertension Molecular Medicine bcl-Associated Death Protein Microtubule-Associated Proteins Signal Transduction medicine.drug |
Zdroj: | Journal of Cellular and Molecular Medicine |
ISSN: | 1582-1838 |
Popis: | 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%, LVAWd and LVPWd, 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-PKCβ2/α-ERK-c-fos pathway; protected myocardium against apoptosis via Akt-FOXO1, Bcl-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-PKCβ2/α-ERK-c-fos and AKT-FOXO1/Bcl-2/survivin/Caspase3 signaling. Rosuvastatin effectively attenuated the structural changes by reversing the signaling transductions involved. |
Databáze: | OpenAIRE |
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