title: 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.
  
  
  OBJECTIVE
  (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM U 460, Groupe Hospitalier Bichat-Claude Bernard, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Prunier
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Barnabas
authors.initials: B
authors.lastname: Gellen
authors.forename: Michèle
authors.initials: M
authors.lastname: Heimburger
authors.forename: Christine
authors.initials: C
authors.lastname: Choqueux
authors.forename: Brigitte
authors.initials: B
authors.lastname: Escoubet
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Mercadier
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015854:Up-Regulation / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000235:genetics*; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases