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혈관 연구단
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Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction

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Title
Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction
Author(s)
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
Publication Date
2018-11
Journal
JOURNAL OF CLINICAL INVESTIGATION, v.128, no.11, pp.5018 - 5033
Publisher
AMER SOC CLINICAL INVESTIGATION INC
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 ��5��1 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
URI
https://pr.ibs.re.kr/handle/8788114/5059
ISSN
0021-9738
Appears in Collections:
Center for Cardiovascular Research(혈관 연구단) > Journal Papers (저널논문)
Files in This Item:
99659.2-20181024140237-covered-253bed37ca4c1ab43d105aefdf7b5536.pdfDownload

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