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.

METHODS AND 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: Yong Wang, Monique C de Waard, Anja Sterner-Kock, Holger Stepan, Heinz-Peter Schultheiss, Dirk J Duncker, Thomas Walther
• Journal: European journal of heart failure (Eur J Heart Fail) 2007 Jun-Jul Vol. 9 Issue 6-7 Pg. 548-57 ISSN: 1388-9842 [Print] England
• PMID: 17407830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Natriuretic Peptide, C-Type

Topics

• Animals
• Gene Expression (physiology)
• Heart Failure (genetics, pathology)
• Heart Ventricles (pathology)
• Hypertrophy, Left Ventricular (genetics, pathology)
• Hypertrophy, Right Ventricular (genetics, pathology)
• Mice
• Mice, Transgenic
• Myocardial Infarction (genetics, pathology)
• Myocardial Reperfusion Injury (genetics, pathology)
• Myocardium (pathology)
• Myocytes, Cardiac (pathology)
• Myofibrils (pathology)
• Natriuretic Peptide, C-Type (genetics)
• Necrosis
• Ventricular Dysfunction (genetics, pathology)
• Ventricular Remodeling (genetics)