Left ventricular SERCA2a gene down-regulation does not parallel ANP gene up-regulation during post-MI remodelling in rats.

Abstract:

BACKGROUND:In most animal models of chronic hemodynamic overload of the left ventricle (LV) as well as in human end stage heart failure, the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) mRNA levels are decreased in parallel with increased atrial natriuretic peptide (ANP) mRNA levels. The situation in the remote myocardium following myocardial infarction (MI) is unclear. AIMS:(1) To examine SERCA2a mRNA levels in the non-infarcted LV myocardium of rats at the chronic stage of experimental MI and (2) To examine whether a negative linear correlation exists between SERCA2a and ANP mRNA levels in this model. METHODS:Anesthetized adult male Wistar rats underwent left coronary artery ligation or sham operation. Three months later, the rats were divided into three groups: sham-operated rats (sham, n=21), HF-free rats with MI (non-failing (NF)-MI, n=29) and rats with both MI and HF (congestive heart failure (CHF)-MI, n=14). LV remodelling and function were assessed by echocardiography and hemodynamic measurements. SERCA2a and ANP mRNA levels were determined by Northern and dot blot analysis with specific cDNA probes. RESULTS:LV SERCA2a mRNA levels varied markedly in sham-operated rats (0.9-1.8). Mean ANP mRNA level increased markedly and mean SERCA2a mRNA level decreased moderately in the remote myocardium. In some NF-MI rats, SERCA2a mRNA levels were higher than those in some sham controls. Whereas ANP mRNA levels correlated well with MI severity (r2=0.79, p<0.001), this was not the case for SERCA2a mRNA levels (r2=0.42, p<0.01). We found no negative correlation between ANP and SERCA2a mRNA levels. CONCLUSION:SERCA2a gene down-regulation in the non-infarcted myocardium of rats with MI does not correlate with ANP gene up-regulation, suggesting that the two genes are not antithetically regulated.

journal_name

Eur J Heart Fail

authors

Prunier F,Chen Y,Gellen B,Heimburger M,Choqueux C,Escoubet B,Michel JB,Mercadier JJ

doi

10.1016/j.ejheart.2004.10.007

keywords:

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

739-47

issue

5

eissn

1388-9842

issn

1879-0844

pii

S1388-9842(04)00285-5

journal_volume

7

pub_type

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