All-trans retinoic acid prevents development of cardiac remodeling in aortic banded rats by inhibiting the renin-angiotensin system

Rashmi Choudhary, Ants Palm-Leis, Robert C. Scott, Rakeshwar S. Guleria, Eric Rachut, Kenneth M. Baker, Jing Pan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number2
DOIs
StatePublished - Feb 2008
Externally publishedYes

Fingerprint

Renin-Angiotensin System
Tretinoin
Pressure
Mitogen-Activated Protein Kinase Phosphatases
Up-Regulation
Dual Specificity Phosphatase 1
Gene Expression
Protein Phosphatase 2
Angiotensinogen
Angiotensin Type 1 Receptor
Caspase 9
Brain Natriuretic Peptide
Mitogen-Activated Protein Kinase 1
Atrial Natriuretic Factor
Peptidyl-Dipeptidase A
Renin
Cardiac Myocytes
Constriction
Caspase 3
Angiotensin II

Keywords

  • Apoptosis
  • Cardiac hypertrophy
  • Heart failure
  • Mitogen-activated protein kinases
  • Pressure overload

ASJC Scopus subject areas

  • Physiology

Cite this

All-trans retinoic acid prevents development of cardiac remodeling in aortic banded rats by inhibiting the renin-angiotensin system. / Choudhary, Rashmi; Palm-Leis, Ants; Scott, Robert C.; Guleria, Rakeshwar S.; Rachut, Eric; Baker, Kenneth M.; Pan, Jing.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 294, No. 2, 02.2008.

Research output: Contribution to journalArticle

Choudhary, Rashmi ; Palm-Leis, Ants ; Scott, Robert C. ; Guleria, Rakeshwar S. ; Rachut, Eric ; Baker, Kenneth M. ; Pan, Jing. / All-trans retinoic acid prevents development of cardiac remodeling in aortic banded rats by inhibiting the renin-angiotensin system. In: American Journal of Physiology - Heart and Circulatory Physiology. 2008 ; Vol. 294, No. 2.
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AB - 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.

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