Anti-Parstatin Promotes Angiogenesis and Ameliorates Left Ventricular Dysfunction during Pressure Overload.

Unlabelled: Parstatin, a novel protease activated receptor-1 (PAR-1) derived peptide is a potent inhibitor of angiogenesis. We and others have reported that imbalance between angiogenic growth factors and anti-angiogenic factors results in transition from compensatory cardiac hypertrophy to heart failure in a pressure overload condition. Though cardio protective role of parstatin was shown previously in ischemic cardiac injury, its role in pressure overload cardiac injury is yet to unveil. We hypothesize that supplementing anti-parstatin antibody during pressure overload condition augments angiogenesis and ameliorate left ventricular dysfunction and heart failure. To verify this, we created ascending aortic banding in mice to mimic pressure overload condition and then treated mice with anti-parstatin antibody. Left ventricular function was assessed by echocardiography and pressure-volume loop study. Angiogenic growth factors and anti-angiogenic factors along with MMP-2,-9 were evaluated by western blot and immunohistochemistry.

Results: our results showed an improved left ventricular function in anti-parstatin treated aortic banding hearts compared to their corresponding wild type controls. Expression of angiogenic growth factor, VEGF, MMP-2 and CD31 expression was increased in treated aortic banding hearts compared to their corresponding wild type controls. Our results suggest that treating pressure overload mice with anti-parstatin antibody augments angiogenesis and ameliorates left ventricular dysfunction.