Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice
Y Wang, MC de Waard, A Sterner‐Kock… - European journal of …, 2007 - Wiley Online Library
Y Wang, MC de Waard, A Sterner‐Kock, H Stepan, HP Schultheiss, DJ Duncker, T Walther
European journal of heart failure, 2007•Wiley Online LibraryObjective: 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 …
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 …
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.
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