Abstract 728: Cardiomyocyte-Restricted Overexpression of C-type Natriuretic Peptide Prevents Cardiac Hypertrophy Induced by Myocardial Infarction in Mice
A cardioprotective role of infused C-type natriuretic peptide (CNP) was recently implicated in preventing myocardial ischemia/reperfusion (I/R) injury and improving cardiac remodeling after myocardial infarction (MI) in rats. Our study aimed to investigate the effect of cardiomyocyte-specific CNP overexpression on I/R injury and MI using in vivo models in transgenic mice. Mice overexpressing CNP in cardiomyocytes were generated, and elevated CNP expression was characterized on RNA and protein levels through RNase-protection assay and radioimmunoassay, respectively. Three- to five-month-old male transgenic mice (TG) and their age-matched wild-type (WT) littermates were subjected to 1-hour global myocardial ischemia and 23 hours reperfusion or permanent ligation of the coronary artery for three weeks. Infarct size did not differ between the WT and TG groups (WT: 68% ± 8 versus TG: 69% ± 7) in I/R mice. In mice that underwent permanent ligation of the coronary arteries, cardiac hypertrophy was prevented by CNP overexpression three weeks post MI as indicated by left ventricle (LV)/tibia length ratio (ΔLV/tibia: WT: 8.6 ± 1.2 versus TG: 1.8 ± 1.3mg/cm; P < 0.01) as well as right ventricle (RV) to tibia length ratio (ΔRV/tibia: WT: 2.4 ± 0.8 versus TG: −1.4 ± 0.5mg/cm; P < 0.01). Histological analysis revealed, consequently, less muscular degeneration and inflammation in TG mice three weeks post MI, and induction of cardiac fibrosis and impairment in cardiac function was less pronounced in these transgenic animals than in their wild-type controls. These results demonstrate that overexpression of CNP in cardiomyocytes does not effect 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 myocardial infarction or hypertension-induced cardiac hypertrophy.