Dectin-2 Deficiency Modulates Th1 Differentiation and Improves Wound Healing After Myocardial Infarction. Issue 7 (31st March 2017)

• Record Type: Journal Article
• Authors: Yan, Xiaoxiang; Zhang, Hang; Fan, Qin; Hu, Jian; Tao, Rong; Chen, Qiujing; Iwakura, Yoichiro; Shen, Weifeng; Lu, Lin; Zhang, Qi; Zhang, Ruiyan
• Is Part Of: Circulation research. Volume 120:Issue 7(2017)
• Publication Date: 2017-03-31
• Subjects: collagen -- flow cytometry -- myocardial infarction -- Th1 cells -- wound healing; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.116.310260
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : 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 α-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-γ immune reaction, through the enhancement of interleukin-12 production in the heart. Interferon-γ was shown to downregulate transforming growth factor-β–induced expression of α-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. Abstract : Supplemental Digital Content is available in the text.