title: Cardiomyocyte-restricted over-expression of C-type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice.
abstract: OBJECTIVE
  Infused C-type natriuretic peptide (CNP) was recently found to play a cardioprotective role in preventing myocardial ischaemia/reperfusion (I/R) injury and improving cardiac remodelling after myocardial infarction (MI) in rats. Our study aimed to investigate the effect of cardiomyocyte-specific CNP over-expression on I/R injury and MI in transgenic mice.
  
  
  RESULTS
  We generated transgenic (TG) mice over-expressing CNP in cardiomyocytes. Elevated CNP expression on RNA and protein levels was demonstrated by RNase-protection assay and radioimmunoassay. Male TG mice and age-matched wild-type (WT) littermates were subjected to 1-hour global myocardial ischaemia and 23 h of reperfusion or permanent ligation of the coronary artery for 3 weeks. Infarct size did not differ between the WT and TG groups in mice subjected to I/R. In mice that underwent permanent ligation of coronary arteries, both left and right ventricular hypertrophy were prevented by CNP over-expression 3 weeks post-MI. Histological analysis revealed less necrosis, muscular degeneration and inflammation in infarcted TG mice. Impairment of cardiac function was less pronounced in transgenic animals than in the wild-type controls.
  
  
  CONCLUSIONS
  Over-expression of CNP in cardiomyocytes does not affect I/R-induced infarct size but prevents cardiac hypertrophy induced by MI. Therefore, CNP may represent a potent therapeutic target for the treatment of patients with cardiac hypertrophy induced by myocardial infarction or other aetiology.
authors.affiliation: Department Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Monique C
authors.initials: MC
authors.lastname: de Waard
authors.forename: Anja
authors.initials: A
authors.lastname: Sterner-Kock
authors.forename: Holger
authors.initials: H
authors.lastname: Stepan
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000502:physiology*; D006333:Heart Failure / Q000235:genetics / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology*; D009210:Myofibrils / Q000473:pathology; D020098:Natriuretic Peptide, C-Type / Q000235:genetics*; D009336:Necrosis; D018754:Ventricular Dysfunction / Q000235:genetics / Q000473:pathology; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D020098:Natriuretic Peptide, C-Type