Blockade of EMAP II protects cardiac function after chronic myocardial infarction by inducing angiogenesis

Chujun Yuan, Lin Yan, Pallavi Solanki, Stephen F. Vatner, Dorothy E. Vatner, Margaret Schwarz

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)224-231
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume79
DOIs
StatePublished - Feb 1 2015

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Myocardial Infarction
Immunoglobulin G
Muscle Cells
Cicatrix
Fibrosis
small inducible cytokine subfamily E, member 1
Antibodies
Coronary Occlusion
Stroke Volume
Myocardial Ischemia
Neoplasms
Coronary Vessels
Proteins
Endothelial Cells
Heart Failure
Biomarkers
Cytokines
Wounds and Injuries

Keywords

  • Angiogenesis
  • Cardioprotection
  • EMAP II inhibition
  • Myocardial infarction

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Blockade of EMAP II protects cardiac function after chronic myocardial infarction by inducing angiogenesis. / Yuan, Chujun; Yan, Lin; Solanki, Pallavi; Vatner, Stephen F.; Vatner, Dorothy E.; Schwarz, Margaret.

In: Journal of Molecular and Cellular Cardiology, Vol. 79, 01.02.2015, p. 224-231.

Research output: Contribution to journalArticle

Yuan, Chujun ; Yan, Lin ; Solanki, Pallavi ; Vatner, Stephen F. ; Vatner, Dorothy E. ; Schwarz, Margaret. / Blockade of EMAP II protects cardiac function after chronic myocardial infarction by inducing angiogenesis. In: Journal of Molecular and Cellular Cardiology. 2015 ; Vol. 79. pp. 224-231.
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AB - 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.

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