Document Detail


Atorvastatin reverses cardiac remodeling possibly through regulation of protein kinase D/myocyte enhancer factor 2D activation in spontaneously hypertensive rats.
MedLine Citation:
PMID:  19683055     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study was designed to determine whether atorvastatin reduced hypertension-induced cardiac remodeling and whether these effects involved Protein Kinase D (PKD) and Myocyte Enhancer Factor 2D (MEF2D), factors known to be implicated in cardiac hypertrophy and fibrosis. 16-Week-old spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats were included. Blood pressure and serum lipid concentration were measured. H-E staining, myocardial transverse diameter, and echocardiography were examined to evaluate cardiac hypertrophy. Hydroxyproline content assay and Masson's trichrome staining were used to estimate cardiac fibrosis. Atorvastatin (10, 25 and 50mg/kg/day) was administered for 8 weeks. Increased blood pressure and cardiac remodeling were prominent in SHRs compared with WKY rats. SHRs also had elevated PKD and MEF2D activation. The systolic blood pressure, myocardial transverse diameter and hydroxyproline content were positively correlated with the activation level of PKD and MEF2D in SHRs. Atorvastatin significantly attenuated the activation of PKD and MEF2D. It may be concluded that atorvastatin reverses hypertension-induced cardiac remodeling partially through down-regulation of PKD/MEF2D activation. Our results predict novel therapeutic targets for atorvastatin in treating hypertensive patients.
Authors:
Jing Geng; Zhuo Zhao; Weiqiang Kang; Wei Wang; Yun Zhang; G E Zhiming
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-13
Journal Detail:
Title:  Pharmacological research : the official journal of the Italian Pharmacological Society     Volume:  61     ISSN:  1096-1186     ISO Abbreviation:  Pharmacol. Res.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-04-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8907422     Medline TA:  Pharmacol Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  40-7     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ltd. All rights reserved.
Affiliation:
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012, PR China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Disease Models, Animal
Enzyme Activation
Fibrosis
Heptanoic Acids / pharmacology*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Hydroxyproline / metabolism
Hypertension / complications,  drug therapy*,  enzymology,  physiopathology
Hypertrophy, Left Ventricular / drug therapy*,  enzymology,  etiology,  physiopathology
Lipids / blood
Male
Myocardium / enzymology*,  pathology
Protein Kinase C / metabolism*
Pyrroles / pharmacology*
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Signal Transduction / drug effects
Time Factors
Transcription Factors / metabolism*
Ventricular Remodeling / drug effects*
Chemical
Reg. No./Substance:
0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Lipids; 0/MEF2D protein, rat; 0/Pyrroles; 0/Transcription Factors; 110862-48-1/atorvastatin; 51-35-4/Hydroxyproline; EC 2.7.10.-/protein kinase D; EC 2.7.11.13/Protein Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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