Nonclassical resident macrophages are important determinants in the development of myocardial fibrosis.

摘要: Macrophages are increasingly recognized as a potential therapeutic target in myocardial fibrosis via interactions with fibroblasts. We have characterized macrophage depletion and inhibition of nonclassical migration, addition to direct between macrophages fibroblasts angiotensin II (AngII)-mediated, hypertensive fibrosis. Macrophage was achieved by daily i.v. clodronate liposomes (−1 day +3 days) during AngII infusion. Cx3cr1 −/− mice were used inhibit migration. phenotype (F4/80, CD11b, Ly6C) immunofluorescence flow cytometry. Collagen assessed Sirius Red/Fast Green. Quantitative real-time RT-PCR performed for transcript levels. AngII/wild-type (WT) displayed significant infiltrate compared saline/WT, which virtually ablated independent hypertension. In vitro data supported M2 promoting fibroblast differentiation collagen production. AngII/ mice, however, significantly increased relative AngII/WT. also showed an M1 phenotypic shift WT in, the predominant Ly6C low , CD206 + (M2). Myocardial IL-1β up-regulated, whereas transforming growth factor β down-regulated this shift. demonstrated that infiltrating critical AngII-mediated preventing development after liposomal circulating monocytes. Our findings suggest some macrophages, namely M2, may confer protective environment prevent excessive tissue injury.