title: MicroRNA Let-7i negatively regulates cardiac inflammation and fibrosis.
abstract: Angiotensin II stimulates fibroblast proliferation and substantially alters gene expression patterns leading to cardiac remodeling, but the mechanisms for such differences are unknown. MicroRNAs are a novel mechanism for gene expression regulation. Herein, we tested the miRNA and mRNA expression patterns in mouse heart using microarray assay and investigated their role in angiotensin II-induced cardiac remodeling. We found that let-7i was dynamically downregulated in angiotensin II-infused heart at day 3 and 7 and had the most targets that were mainly associated with cardiac inflammation and fibrosis. Overexpression or knockdown of let-7i in cultured cardiac fibroblasts demonstrated that let-7i played an inhibitory effect on the expression of its targets interleukin-6 and collagens. Furthermore, delivery of let-7i to mouse significantly inhibited angiotensin II-induced cardiac inflammation and fibrosis in a dose-dependent manner. Conversely, knockdown of let-7i aggravated this effect. Together, our results clearly demonstrate that let-7i acts as a novel negative regulator of angiotensin II-induced cardiac inflammation and fibrosis by suppressing the expression of interleukin-6 and multiple collagens in the heart and may represent a new potential therapeutic target for treating hypertensive cardiac fibrosis.
authors.affiliation: From the Department of Pathology and Pathophysiology, School of Basic Medical Sciences (X.W., H.-X.W., C.-Y.Z., H.-H.L.) and Beijing AnZhen Hospital, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases (Y.-L.L., C.-C.Z., J.D., H.-H.L.), Capital Medical University, Beijing, China; and Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China (L.W., Y.-L.X.).
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: From the Department of Pathology and Pathophysiology, School of Basic Medical Sciences (X.W., H.-X.W., C.-Y.Z., H.-H.L.) and Beijing AnZhen Hospital, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases (Y.-L.L., C.-C.Z., J.D., H.-H.L.), Capital Medical University, Beijing, China; and Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China (L.W., Y.-L.X.).
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.affiliation: From the Department of Pathology and Pathophysiology, School of Basic Medical Sciences (X.W., H.-X.W., C.-Y.Z., H.-H.L.) and Beijing AnZhen Hospital, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases (Y.-L.L., C.-C.Z., J.D., H.-H.L.), Capital Medical University, Beijing, China; and Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China (L.W., Y.-L.X.).
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Li
authors.affiliation: From the Department of Pathology and Pathophysiology, School of Basic Medical Sciences (X.W., H.-X.W., C.-Y.Z., H.-H.L.) and Beijing AnZhen Hospital, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases (Y.-L.L., C.-C.Z., J.D., H.-H.L.), Capital Medical University, Beijing, China; and Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China (L.W., Y.-L.X.).
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: Zhang
authors.affiliation: From the Department of Pathology and Pathophysiology, School of Basic Medical Sciences (X.W., H.-X.W., C.-Y.Z., H.-H.L.) and Beijing AnZhen Hospital, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases (Y.-L.L., C.-C.Z., J.D., H.-H.L.), Capital Medical University, Beijing, China; and Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China (L.W., Y.-L.X.).
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Zhou
authors.affiliation: From the Department of Pathology and Pathophysiology, School of Basic Medical Sciences (X.W., H.-X.W., C.-Y.Z., H.-H.L.) and Beijing AnZhen Hospital, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases (Y.-L.L., C.-C.Z., J.D., H.-H.L.), Capital Medical University, Beijing, China; and Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China (L.W., Y.-L.X.).
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: From the Department of Pathology and Pathophysiology, School of Basic Medical Sciences (X.W., H.-X.W., C.-Y.Z., H.-H.L.) and Beijing AnZhen Hospital, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases (Y.-L.L., C.-C.Z., J.D., H.-H.L.), Capital Medical University, Beijing, China; and Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China (L.W., Y.-L.X.). hhli1995@aliyun.com jdu@bcm.edu yunlong_xia@126.com.
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Xia
authors.affiliation: From the Department of Pathology and Pathophysiology, School of Basic Medical Sciences (X.W., H.-X.W., C.-Y.Z., H.-H.L.) and Beijing AnZhen Hospital, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases (Y.-L.L., C.-C.Z., J.D., H.-H.L.), Capital Medical University, Beijing, China; and Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China (L.W., Y.-L.X.). hhli1995@aliyun.com jdu@bcm.edu yunlong_xia@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: From the Department of Pathology and Pathophysiology, School of Basic Medical Sciences (X.W., H.-X.W., C.-Y.Z., H.-H.L.) and Beijing AnZhen Hospital, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases (Y.-L.L., C.-C.Z., J.D., H.-H.L.), Capital Medical University, Beijing, China; and Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China (L.W., Y.-L.X.). hhli1995@aliyun.com jdu@bcm.edu yunlong_xia@126.com.
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009205:Myocarditis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D040081:Protein Array Analysis; D012313:RNA / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C542687:mirnlet7 microRNA, mouse; D012313:RNA
keywords: angiotensin II; collagen; inflammation; interleukin-6; microRNAs