Authors: Bijun Chen, Ya Su, Nikolaos G Frangogiannis
Published: 2020-10-27
DOI: 10.1161/res.127.suppl_1.mp152
Source: Full article
Macrophages play multiple roles in repair and remodeling of the infarcted heart, contributing to phagocytosis of dead cells, regulation of inflammation, fibrosis and angiogenesis. TGF-β superfamily members are critically involved in regulation of macrophage phenotype through the Smad cascades. In most cell types, TGF-βs signal predominantly by activating Smad2/3 signaling, whereas BMPs act through Smad1/5-mediated pathways. We previously showed that TGF-β/Smad3 signaling in macrophages protects the infarcted heart from adverse remodeling by mediating phagocytotic activity and anti-inflammatory transition. However, the in vivo role of Smad1/5 signaling in macrophages remains unknown. We examined the role of macrophage-specific Smad1 signaling in a mouse model of myocardial infarction (MI). Smad1 is activated in a subset of myeloid cells infiltrating the infarcted myocardium. In vitro, TGF-β1, TGF-β3, BMP4, BMP7, but not TGF-β2, BMP2, BMP6 markedly activated Smad1/5 signaling in macrophages. In order to examine the role of Smad1 in regulation of macrophage phenotype we generated myeloid cell-specific Smad1 KO mice (MyS1KO). MyS1KO mice had better survival compared to S1fl/fl controls 28 days post MI (