Abstract 11070: A Critical Role of Salusin-β in Suppressing Angiogenesis After Myocardial Infarction and Ischemia Reperfusion Injury
Background: Salusins are multifunctional endogenous bioactive peptides biosynthesized simultaneously from their precursor prosalusin. Salusin-β stimulates proliferation of vascular smooth muscle cells (VSMCs) and fibroblasts, and regulates myocardial growth and hypertrophy. Salusin-β has potent hypotensive, bradycardic and proatherosclerotic effects. However, it remains uninvestigated whether salusin-β plays any role in myocardial remodeling after myocardial infarction (MI) and ischemia reperfusion (I/R) injury.
Hypothesis: We assessed the hypothesis that salusin-β could attenuate LV remodeling after myocardial ischemia.
Methods and Results: Rat MI and I/R models were created by LAD ligation for 4 weeks (MI, n=5 each) or occluded for 30 minutes, followed by 24 hours or 7 days of reperfusion (I/R, n=6 each). Immunohistochemical double staining showed the enhanced expression of salusin-β in the macrophages around the myocardial ischemic area. Anti-salusin-β treated groups were administered with the neutralizing salusin-β antibody (10 ml/day, i.p.) once daily from day -1 to 28 (MI, n=9), from day -1 to 1 or from day -1 to 7 (I/R, n=6, each). In the MI models, the anti-salusin-β therapy significantly improved left ventricular ejection fraction compared to the control group on day 7 (71.9±3.3 % vs. 42.0±1.5 %, p<0.05) and day 28 (60.7±3.8 % vs. 37.2±2.0 %, p<0.05). In the model, the anti-salusin-β treatment prevented mean blood pressure decline on day 7 (79.8±2.2 mmHg vs. 70.8±2.0 mmHg, p<0.05) and day 14 (82.0±1.6 mmHg vs. 73.2±3.3 mmHg, p<0.05). Furthermore, anti-salusin-β therapy enhanced myocardial angiogenesis in the peri-ischemic area of reperfusion of I/R models. The small vessels (less than 40 micro m diameter) of I/R hearts treated with anti-salusin-β were more densely populated than those of control animals (108.5±19.7 vs. 47.5±2.4, p<0.01). Real-time RT-PCR revealed that the anti-salusin-β therapy-induced angiogenesis was not associated with enhanced VEGF expression.
Conclusions: We, for the first time, clarified that endogenous salusin-β suppresses angiogenesis/ventricular remodeling which is critical in restoring cardiac function following MI and I/R injury.
- © 2010 by American Heart Association, Inc.