Abstract 18312: In vivo Selection of Ghrelin as a Powerful Cardioprotective Factor After Myocardial Infarction
Introduction: By applying an innovative selection procedure based on in vivo gene transfer of AAV libraries coding for the entire mouse secretome, we discovered that the neurohormone ghrelin exerts a powerful protective effect against skeletal muscle damage. In particular, an AAV9 expressing ghrelin protected muscle fibers from severe hind limb ischemia and promoted muscle regeneration.
Hypothesis: Based on the established similarities between biology and functional regulation of cardiomyocytes and muscle cells, we wanted to assess the hypothesis that ghrelin was also an effective protective factor in a mouse model of myocardial infarction (MI).
Methods: A group of CD1 mice (n=20 per group) underwent permanent left descendent coronary artery ligation and were immediately injected into the peri-infarcted area with 1x10^11 viral particles of an AAV9 vector expressing ghrelin or a control AAV9 empty vector. Cardiac function after MI was monitored by echocardiography, morphometric, histological and molecular analysis.
Results: Cardiac gene delivery of AAV9-Ghrelin after MI determined a marked improvement of cardiac function (LVEF: 51±3% vs. 31±3% for AAV9-Ghrelin vs. AAV9-Control vector; LVFS: 26±1% vs. 15±2%) at day 90 after MI (p<0.001 in both cases), while significantly reducing infarct size (27±2 vs. 51±5%; p<0.001). The marked improvement in cardiac contractility was paralleled by a reduced apoptotic rate at early times after MI (31±5% vs 8±4%, p<0.005) and reduced inflammatory cells infiltration in the peri-infarctual region. Moreover, ghrelin counteracted the induction of markers of cardiac damage (in particular, miR21 and MMP-2) and prevented the deregulated expression of pathological left ventricle remodelling markers, such ad bMHC, BNP and others.
Conclusions: In conclusion, these results demonstrate the efficacy of ghrelin as a powerful molecule conferring protection from skeletal muscle degeneration and providing benefit upon cardiac damage.
- © 2013 by American Heart Association, Inc.