title: Macrophage-Derived mir-155-Containing Exosomes Suppress Fibroblast Proliferation and Promote Fibroblast Inflammation during Cardiac Injury.
abstract: Inflammation plays an important role in cardiac injuries. Here, we examined the role of miRNA in regulating inflammation and cardiac injury during myocardial infarction. We showed that mir-155 expression was increased in the mouse heart after myocardial infarction. Upregulated mir-155 was primarily presented in macrophages and cardiac fibroblasts of injured hearts, while pri-mir-155 was only expressed in macrophages. mir-155 was also presented in exosomes derived from macrophages, and it can be transferred into cardiac fibroblasts by macrophage-derived exosomes. A mir-155 mimic or mir-155 containing exosomes inhibited cardiac fibroblast proliferation by downregulating Son of Sevenless 1 expression and promoted inflammation by decreasing Suppressor of Cytokine Signaling 1 expression. These effects were reversed by the addition of a mir-155 inhibitor. In vivo, mir-155-deficient mice showed a significant reduction of the incidence of cardiac rupture and an improved cardiac function compared with wild-type mice. Moreover, transfusion of wild-type macrophage exosomes to mir-155-/-mice exacerbated cardiac rupture. Finally, the mir-155-deficient mice exhibited elevated fibroblast proliferation and collagen production, along with reduced cardiac inflammation in injured heart. Taken together, our results demonstrate that activated macrophages secrete mir-155-enriched exosomes and identify macrophage-derived mir-155 as a paracrine regulator for fibroblast proliferation and inflammation; thus, a mir-155 inhibitor (i.e., mir-155 antagomir) has the potential to be a therapeutic agent for reducing acute myocardial-infarction-related adverse events.
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Luxin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Xi
authors.initials: X
authors.lastname: A
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Boya
authors.initials: B
authors.lastname: Chen
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China. Electronic address: lyllyl_1111@163.com.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China. Electronic address: jdu@bcm.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D002450:Cell Communication; D049109:Cell Proliferation; D004195:Disease Models, Animal; D055354:Exosomes / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006342:Heart Rupture, Post-Infarction / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D034622:RNA Interference; D034443:RNA Transport; D020837:SOS1 Protein / Q000235:genetics
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D020837:SOS1 Protein
keywords: cardiac fibroblast; inflammation; mir-155; myocardial infarction; proliferation