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
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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