© 2004 European Society of Cardiology
Left ventricular SERCA2a gene down-regulation does not parallel ANP gene up-regulation during post-MI remodelling in rats
a INSERM U 460, Groupe Hospitalier Bichat-Claude Bernard, Paris, France
b INSERM U 426, Faculté de Médecine Xavier Bichat, CEFI, IFR 02, Faculté de Médecine Xavier Bichat, Paris, France, Service de Physiologie—Explorations Fonctionnelles, Groupe Hospitalier Bichat-Claude Bernard, A.P.-H.P., Paris, France
* Corresponding author. Tel.: +33 1 40 25 86 08; fax: +33 1 40 25 86 02. E-mail address:jjmercadier{at}wanadoo.fr
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Abstract |
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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.
Key Words: Sarcoplasmic reticulum calcium-ATPase • Atrial natriuretic peptide • Myocardial infarction • Heart failure
Received April 19, 2004; Revised July 14, 2004; Accepted October 14, 2004
1 Current address: Laboratoire de Préconditionnement et Remodelage du Myocarde, Angers, France.
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