Effect of lipid factor CTRP9 on myocardial remodeling induced by isoproterenol in mice

Objective To investigate the effect of lipid factor CTRP9 on myocardial remodeling induced by isoproterenol in mice. Methods Male C57BL/6J mice were randomly assigned to four groups (n=10 per group), then mice were administered 5 mg/kg ISO q12h for 12 days by daily subcutaneous injection to induce myocardial remodeling model. Mice also received subcutaneous injection of CTRP9 (200 μg·kg-1·d-1) for 12days. Echocardiography was performed to compare the ventricular wall thickness and cardiac function. Heart weight/body weight (HW/BW), lung weight/body weight (LW/BW), heart weight/tibia length (HW/TL) and cross-sectional area of cardiomyocytes were compared between groups. The cardiac hypertrophic markers and fibrotic markers were also compared by RT-PCR between the two groups. Molecular protein changes were evaluated by Western blot. Results CTRP9 was down-regulated in model group. The LVEDd (4.00 mm vs 4.67 mm), LVEDs (2.60 mm vs 3.12 mm) in mode group were both higher than control group while the LVEF (73% vs 55%) and FS (39% vs 21%) were reduced in mode group. Compared with the control group, the HW/BW, LW/BW, HW/TL and cross-sectional area of cardiomyocytes were much higher in mode group (P<0.05). The transcription level of hypertrophic markers (ANP, BNP, β-MHC) were elevated. Left ventricular collagen volume was increased as well as the transcription level of fibrosis markers collagen Ⅰ, collagen Ⅲ and a-SMA. Western blot results indicated that CTRP9 increased nNOS and eNOS derived NO production but not iNOS expression. Conclusion CTRP9 could protect against ISO induced myocardial remodeling by increasing nNOS and eNOS derived NO production. Key words: Isoproterenol; Cardiac remodeling; Adipose factor; Nitric oxide synthase