| First Author | Yan X | Year | 2017 |
| Journal | Circ Res | Volume | 120 |
| Issue | 7 | Pages | 1116-1129 |
| PubMed ID | 28193608 | Mgi Jnum | J:262031 |
| Mgi Id | MGI:6156746 | Doi | 10.1161/CIRCRESAHA.116.310260 |
| Citation | Yan X, et al. (2017) Dectin-2 Deficiency Modulates Th1 Differentiation and Improves Wound Healing After Myocardial Infarction. Circ Res 120(7):1116-1129 |
| abstractText | 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 alpha-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-beta-induced expression of alpha-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. |
