Abstract 21641: Blocking Endothelial-Monocyte-Activating-Polypeptide-II Improves Remodeling After Chronic Myocardial Infarction by Promoting Angiogenesis
Endothelial-monocyte-activating-polypeptide-II (EMAP-II) is a pro-inflammatory cytokine with anti-angiogenic properties. We examined whether blocking the effects of EMAP-II with a functional blocking antibody of EMAP-II (EMAP-II AB) affected myocardial remodeling and angiogenesis following chronic myocardial infarction (MI). C57BL/6J mice received either a control vehicle (IgG) or EMAP-II AB via i.p. injection after MI. At 4 weeks after MI, LV function, assessed by LV ejection fraction (EF), was reduced in the vehicle group (35±2%, n=7) compared with sham operated controls (72±1%, n=4). Blocking EMAP-II preserved LV EF (53±4%, n=10) compared with vehicle group, p<0.05. The interstitial collagen (%) was examined by Picric Acid Sirius Red staining. Blocking EMAP-II reduced the amount of interstitial fibrosis (4.8±0.5%) compared to the vehicle group (7.6±0.7%). Since % survival was greater in EMAP-II AB treated group (57%) than in the vehicle group (36%), it is likely that the above data underestimated the beneficial effects of blocking EMAP-II, since the animals that died presumably exhibited more severe cardiac dysfunction and fibrosis. Immunostaining for Ki67-positive endothelial cells (isolectin), used as an index of angiogenesis, demonstrated more Ki-67 positive endothelial cells in the EMAP-II AB group (63±4.0/mm2) vs the vehicle group (47±5.4/mm2). Furthermore, there was a highly significant positive correlation (R2=0.951) between the number of Ki67-positive endothelial cells and the improvement in LV EF. Capillary density(%) was also increased by EMAP-II AB (30±1.4%) compared with the vehicle group (24±0.4%). Thus, blocking EMAP-II significantly improves myocardial remodeling after chronic MI, as reflected by improved cardiac function and reduced fibrosis. The increased Ki67 positive endothelial cells and capillary density suggest that angiogenesis is involved in the mechanism.
- © 2010 by American Heart Association, Inc.