Document Detail


All-trans retinoic acid prevents development of cardiac remodeling in aortic banded rats by inhibiting the renin-angiotensin system.
MedLine Citation:
PMID:  18156191     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study was designed to determine the effect of all-trans retinoic acid (RA) on the development of cardiac remodeling in a pressure overload rat model. Male Sprague-Dawley rats were subjected to sham operation and the aortic constriction procedure. A subgroup of sham control and aortic constricted rats were treated with RA for 5 mo after surgery. Pressure-overloaded rats showed significantly increased interstitial and perivascular fibrosis, heart weight-to-body weight ratio, and gene expression of atrial natriuretic peptide and brain natriuretic peptide. Echocardiographic analysis showed that pressure overload induced systolic and diastolic dysfunction, as evidenced by decreased fractional shortening, ejection fraction, stroke volume, and increased E-to-E(a) ratio and isovolumic relaxation time. RA treatment prevented the above changes in cardiac structure and function and hypertrophic gene expression in pressure-overloaded rats. RA restored the ratio of Bcl-2 to Bax, inhibited cleavage of caspase-3 and -9, and prevented the decreases in the levels of SOD-1 and SOD-2. Pressure overload-induced phosphorylation of ERK1/2, JNK, and p38 was inhibited by RA, via upregulation of mitogen-activated protein kinase phosphatase (MKP)-1 and MKP-2. The pressure overload-induced production of angiotensin II was inhibited by RA via upregulation of expression of angiotensin-converting enzyme (ACE)2 and through inhibition of the expression of cardiac and renal renin, angiotensinogen, ACE, and angiotensin type 1 receptor. Similar results were observed in cultured neonatal cardiomyocytes in response to static stretch. These results demonstrate that RA has a significant inhibitory effect on pressure overload-induced cardiac remodeling, through inhibition of the expression of renin-angiotensin system components.
Authors:
Rashmi Choudhary; Ants Palm-Leis; Robert C Scott; Rakeshwar S Guleria; Eric Rachut; Kenneth M Baker; Jing Pan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-21
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  294     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-12     Completed Date:  2008-03-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H633-44     Citation Subset:  IM    
Affiliation:
Department of Renal Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Aorta, Thoracic / physiology*
Apoptosis / drug effects
Atrial Natriuretic Factor / pharmacology
Blood Pressure / drug effects
Blotting, Western
Cells, Cultured
Fibrosis / prevention & control
Heart / drug effects*
Heart Rate / drug effects
Hypertrophy, Left Ventricular / prevention & control,  ultrasonography
Ligation
Male
Mitogen-Activated Protein Kinases / physiology
Myocardium / pathology
Myocytes, Cardiac / drug effects
Natriuretic Peptide, Brain / pharmacology
Physical Stimulation
Rats
Rats, Sprague-Dawley
Renin-Angiotensin System / drug effects*
Reverse Transcriptase Polymerase Chain Reaction
Tretinoin / pharmacology*,  therapeutic use
Chemical
Reg. No./Substance:
114471-18-0/Natriuretic Peptide, Brain; 302-79-4/Tretinoin; 85637-73-6/Atrial Natriuretic Factor; EC 2.7.11.24/Mitogen-Activated Protein Kinases
Comments/Corrections
Comment In:
Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H588-9   [PMID:  18178713 ]

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


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