P1264
Cardioprotective effects of a novel designer C-type natriuretic peptide-based therapeutic, C53, for the prevention of post-myocardial infarction heart failure

Extract

Background: Cardiac dysfunction and remodeling after myocardial infarction (MI) is a leading cause of heart failure (HF) and death. Despite therapeutic advances, many patients progress to post-MI HF and thus there is an urgent need for the development of novel therapeutic approaches. C-type natriuretic peptide (CNP) possesses potent cardioprotective properties such as reducing adverse cardiac remodeling and functional impairment. However, the therapeutic actions of native CNP are limited due to rapid degradation by neprilysin (NEP). Therefore, we designed a novel CNP-based therapeutic, C53, that is resistant to NEP degradation which is supported by our preliminary studies. Here we sought to advance its therapeutic potential in vivo by testing the hypothesis that C53 has cardioprotective actions in experimental MI.

Methods: Sprague-Dawley rats underwent left coronary artery ligation to induce MI and cardiac dysfunction. One weeks after recovery, MI rats (n=18) were randomized into 2 groups: MI-vehicle (MI-V) or MI-C53. Vehicle (5% dextrose) or C53 (0.264 ug/kg/min) was given via subcutaneous (SQ) minipump for 4 weeks. LV ejection fraction (EF) and fractional shortening (FS) was assessed at 1 week after MI induction prior to treatment (BL) and at 2 and 4 weeks after vehicle or C53 treatment. At 4 weeks heart weight (HW), total lung weight (TLW) and mean arterial blood pressure (MABP) were also assessed. Data are presented as mean ±SEM. * p<0.05 vs MI-V.