期刊
CIRCULATION RESEARCH
卷 120, 期 7, 页码 1116-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.116.310260
关键词
collagen; flow cytometry; myocardial infarction; Th1 cells; wound healing
资金
- 973 grant from National Science and Technology [2015CBS553604]
- National Natural Science Foundation of China [81570316, 81400362, 81670457, 91539117, 81470392]
- Shanghai Rising-Star Program grant [17QA1402300]
- Grants-in-Aid for Scientific Research [15H05787] Funding Source: KAKEN
Rationale: Macrophages are involved in wound healing after myocardial infarction (MI). The role of Dectin-2, a pattern recognition receptor mainly expressed on myeloid cells, in the infarct healing remains unknown. Objective: The aim of this study is to determine whether Dectin-2 signaling is involved in the healing process and cardiac remodeling after MI and to elucidate the underlying molecular mechanisms. Methods and Results: In a mouse model of permanent coronary ligation, Dectin-2, mainly expressed in macrophages, was shown to be increased in the early phase after MI. Dectin-2 knockout mice showed an improvement in the infarct healing and cardiac remodeling, compared with wild-type mice, which was demonstrated by significantly lower mortality because of cardiac rupture, increased wall thickness, and better cardiac function. Increased expression of a-smooth muscle actin and collagen I/III was observed, whereas the levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 were decreased in the hearts of Dectin-2 knockout mice after MI. Dectin-2 deficiency inhibited the rate of apoptotic and necrotic cell death. However, Dectin-2 did not affect immune cell infiltration and macrophage polarization, but it led to a stronger activation of the Th1/interferon-gamma immune reaction, through the enhancement of interleukin-12 production in the heart. Interferon-gamma was shown to downregulate transforming growth factor-alpha-induced expression of a-smooth muscle actin and collagen I/III in isolated cardiac fibroblasts, leading to a decrease in migration and myofibroblast differentiation. Finally, Dectin-2 knockout improved myocardial ischemia-reperfusion injury and infarct healing. Conclusions: Dectin-2 leads to an increase in cardiac rupture, impairs wound healing, and aggravates cardiac remodeling after MI through the modulation of Th1 differentiation.
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