Promoting angiogenesis is a key therapeutic target for protection from chronic ischemic cardiac injury.
Endothelial-Monocyte-Activating-Polypeptide-II (
EMAP II)
protein, a tumor-derived
cytokine having anti-angiogenic properties in
cancer, is markedly elevated following
myocardial ischemia. We examined whether neutralization of
EMAP II induces angiogenesis and has beneficial effects on myocardial function and structure after chronic
myocardial infarction (MI).
EMAP II antibody (
EMAP II AB), vehicle, or non-specific
IgG (
IgG) was injected ip at 30 min and 3, 6, and 9 days after permanent coronary artery occlusion in mice.
EMAP II AB, compared with vehicle or non-specific antibody, significantly, p<0.05, improved the survival rate after MI, reduced
scar size and attenuated the development of
heart failure, i.e., left ventricular ejection fraction was significantly higher in
EMAP II AB group,
fibrosis was reduced by 24%, and importantly, more myocytes were alive in
EMAP II AB group in the
infarct area. In support of an angiogenic mechanism, capillary density (193/HPF vs. 172/HPF), doubling of the number of proliferating endothelial cells, and angiogenesis related
biomarkers were upregulated in mice receiving
EMAP II AB treatment as compared to
IgG. Furthermore,
EMAP II AB prevented
EMAP II protein inhibition of in vitro tube formation in HUVECs. We conclude that blockade of
EMAP II induces angiogenesis and improves cardiac function following chronic MI, resulting in reduced myocardial
fibrosis and
scar formation and increased capillary density and preserved viable myocytes in the
infarct area.