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Left ventricular SERCA2a gene down‐regulation does not parallel ANP gene up‐regulation during post‐MI remodelling in rats
Author(s) -
Prunier Fabrice,
Chen Ying,
Gellen Barnabas,
Heimburger Michéle,
Choqueux Christine,
Escoubet Brigitte,
Michel JeanBaptiste,
Mercadier JeanJacques
Publication year - 2005
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2004.10.007
Subject(s) - medicine , heart failure , ligation , ventricle , atrial natriuretic peptide , endocrinology , messenger rna , hemodynamics , myocardial infarction , ventricular remodeling , cardiology , gene expression , left coronary artery , biology , gene , biochemistry
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) Ca 2+ ‐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 ( r 2 =0.79, p <0.001), this was not the case for SERCA2a mRNA levels ( r 2 =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.