Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction

Seung Jun Lee, Choong Kun Lee, Seok Kang, Intae Park, Yoo Hyung Kim, Seo Ki Kim, Seon Pyo Hong, Hosung Bae, Yulong He, Yoshiaki Kubota, Gou Young Koh

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Emerging evidence indicates that angiopoietin-2 (Angpt2), a well-recognized vascular destabilizing factor, is a biomarker of poor outcome in ischemic heart disease. However, its precise role in postischemic cardiovascular remodeling is poorly understood. Here, we show that Angpt2 plays multifaceted roles in the exacerbation of cardiac hypoxia and inflammation after myocardial ischemia. Angpt2 was highly expressed in endothelial cells at the infarct border zone after myocardial infarction (MI) or ischemia/reperfusion injury in mice. In the acute phase of MI, endothelial-derived Angpt2 antagonized Angpt1/Tie2 signaling, which was greatly involved in pericyte detachment, vascular leakage, increased adhesion molecular expression, degradation of the glycocalyx and extracellular matrix, and enhanced neutrophil infiltration and hypoxia in the infarct border area. In the chronic remodeling phase after MI, endothelial- and macrophage-derived Angpt2 continuously promoted abnormal vascular remodeling and proinflammatory macrophage polarization through integrin α5β1 signaling, worsening cardiac hypoxia and inflammation. Accordingly, inhibition of Angpt2 either by gene deletion or using an anti-Angpt2 blocking antibody substantially alleviated these pathological findings and ameliorated postischemic cardiovascular remodeling. Blockade of Angpt2 thus has potential as a therapeutic option for ischemic heart failure.

Original languageEnglish
Pages (from-to)5018-5033
Number of pages16
JournalThe Journal of clinical investigation
Volume128
Issue number11
DOIs
Publication statusPublished - 2018 Nov 1

Fingerprint

Angiopoietin-2
Myocardial Infarction
Inflammation
Myocardial Ischemia
Macrophages
Glycocalyx
Pericytes
Blocking Antibodies
Neutrophil Infiltration
Hypoxia
Gene Deletion
Reperfusion Injury
Integrins
Extracellular Matrix
Blood Vessels
Endothelial Cells
Heart Failure
Biomarkers

Keywords

  • Cardiology
  • Cardiovascular disease
  • endothelial cells
  • Pericytes
  • Vascular Biology

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lee, S. J., Lee, C. K., Kang, S., Park, I., Kim, Y. H., Kim, S. K., ... Koh, G. Y. (2018). Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction. The Journal of clinical investigation, 128(11), 5018-5033. https://doi.org/10.1172/JCI99659

Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction. / Lee, Seung Jun; Lee, Choong Kun; Kang, Seok; Park, Intae; Kim, Yoo Hyung; Kim, Seo Ki; Hong, Seon Pyo; Bae, Hosung; He, Yulong; Kubota, Yoshiaki; Koh, Gou Young.

In: The Journal of clinical investigation, Vol. 128, No. 11, 01.11.2018, p. 5018-5033.

Research output: Contribution to journalArticle

Lee, SJ, Lee, CK, Kang, S, Park, I, Kim, YH, Kim, SK, Hong, SP, Bae, H, He, Y, Kubota, Y & Koh, GY 2018, 'Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction', The Journal of clinical investigation, vol. 128, no. 11, pp. 5018-5033. https://doi.org/10.1172/JCI99659
Lee, Seung Jun ; Lee, Choong Kun ; Kang, Seok ; Park, Intae ; Kim, Yoo Hyung ; Kim, Seo Ki ; Hong, Seon Pyo ; Bae, Hosung ; He, Yulong ; Kubota, Yoshiaki ; Koh, Gou Young. / Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction. In: The Journal of clinical investigation. 2018 ; Vol. 128, No. 11. pp. 5018-5033.
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