© 2007 European Society of Cardiology
Cardiomyocyte-restricted over-expression of C-type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice
a Department Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin (CBF), Germany
b Department of Pharmacology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands
c Experimental Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
d Institute for Veterinary Pathology, Freie Universität, Berlin, Germany
e Department of Obstetrics and Gynecology, University of Leipzig, Germany
* Corresponding author. Department of Pharmacology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. Tel.: +31 10 4087530; fax: +31 10 4089458. E-mail address: thomas.walther{at}charite.de
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Abstract |
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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.
Key Words: Natriuretic peptide • Infarction • Hypertrophy • Ischaemia • Reperfusion
Received September 15, 2006; Revised January 16, 2007; Accepted February 19, 2007
1 Both authors contributed equally to this work.
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