Journal article
Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction
The Journal of clinical investigation, Vol.128(11), pp.5018-5033
11/01/2018
DOI: 10.1172/JCI99659
PMID: 30295643
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.
Details
- Title: Subtitle
- Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction
- Creators
- Seung-Jun Lee - Keio UniversityChoong-kun Lee - Keio UniversitySeok Kang - Keio UniversityIntae Park - Korea Advanced Institute of Science and TechnologyYoo Hyung Kim - Korea Advanced Institute of Science and TechnologySeo Ki Kim - Korea Advanced Institute of Science and TechnologySeon Pyo Hong - Institute for Basic ScienceHosung Bae - Korea Advanced Institute of Science and TechnologyYulong He - Soochow UniversityYoshiaki Kubota - Keio UniversityGou Young Koh - Korea Advanced Institute of Science and Technology
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.128(11), pp.5018-5033
- DOI
- 10.1172/JCI99659
- PMID
- 30295643
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Number of pages
- 16
- Grant note
- IBS-R025-D1-2015,G.Y.K. / Institute of Basic Science, Republic of Korea
- Language
- English
- Date published
- 11/01/2018
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985217131802771
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