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Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice
Author(s) -
Wang Yong,
Waard Monique C.,
SternerKock Anja,
Stepan Holger,
Schultheiss HeinzPeter,
Duncker Dirk J.,
Walther Thomas
Publication year - 2007
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2007.02.006
Subject(s) - medicine , myocardial infarction , ligation , cardiology , natriuretic peptide , muscle hypertrophy , endocrinology , genetically modified mouse , infarction , heart failure , transgene , ischemia , atrial natriuretic peptide , biology , biochemistry , gene
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.