ArticleCirculation research2016
Shift of Macrophage Phenotype Due to Cartilage Oligomeric Matrix Protein Deficiency Drives Atherosclerotic Calcification.
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Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
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35 citing papers in PubMed, 66 citations in OpenAlex.
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- Histone Lysine Methylation Modification and Its Role in Vascular Calcification.Frontiers in endocrinology · 2022Review
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- The role of caveolae in endothelial dysfunction.Medical review (2021) · 2021Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Yi FuFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Cheng GaoFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Ying LiangFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Meili WangFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Yaqian HuangFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Wei MaFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Tuoyi LiFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Yiting JiaFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Fang YuFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Wanlin ZhuFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Qinghua CuiFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Yanhui LiFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Qingbo XuFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Xian WangFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.).
Wei KongFrom the Department of Physiology and Pathophysiology (Y.F., C.G., Y.L., M.W., Y.H., T.L., Y.J., F.Y., X.W., W.K.), Department of Biomedical Informatics (W.M., Q.C.), Institute of Cardiovascular Sciences, School of Basic Medical Sciences (Y.L.), Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (Y.F., C.G., Y.L., M.W., Y.H., W.M., T.L., Y.J., F.Y., Q.C., Y.L., X.W., W.K.); School of Biological Science and Medical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, Beijing, P. R. China (W.Z.); and Cardiovascular Division, King's College London BHF Centre, London, United Kingdom (Q.X.). kongw@bjmu.edu.cn.
Ministry of Education of the People's Republic of China · CNBeihang University · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleIntimal calcification is highly correlated with atherosclerotic plaque burden, but the underlying mechanism is poorly understood. We recently reported that cartilage oligomeric matrix protein (COMP), a component of vascular extracellular matrix, is an endogenous inhibitor of vascular smooth muscle cell calcification.
objectiveTo investigate whether COMP affects atherosclerotic calcification. METHODS AND
resultsApoE(-/-)COMP(-/-) mice fed with chow diet for 12 months manifested more extensive atherosclerotic calcification in the innominate arteries than did ApoE(-/-) mice. To investigate which origins of COMP contributed to atherosclerotic calcification, bone marrow transplantation was performed between ApoE(-/-) and ApoE(-/-)COMP(-/-) mice. Enhanced calcification was observed in mice transplanted with ApoE(-/-)COMP(-/-) bone marrow compared with mice transplanted with ApoE(-/-) bone marrow, indicating that bone marrow-derived COMP may play a critical role in atherosclerotic calcification. Furthermore, microarray profiling of wild-type and COMP(-/-) macrophages revealed that COMP-deficient macrophages exerted atherogenic and osteogenic characters. Integrin β3 protein was attenuated in COMP(-/-) macrophages, and overexpression of integrin β3 inhibited the shift of macrophage phenotypes by COMP deficiency. Furthermore, adeno-associated virus 2-integrin β3 infection attenuated atherosclerotic calcification in ApoE(-/-)COMP(-/-) mice. Mechanistically, COMP bound directly to β-tail domain of integrin β3 via its C-terminus, and blocking of the COMP-integrin β3 association by β-tail domain mimicked the COMP deficiency-induced shift in macrophage phenotypes. Similar to COMP deficiency in mice, transduction of adeno-associated virus 2-β-tail domain enhanced atherosclerotic calcification in ApoE(-/-) mice.
conclusionsThese results reveal that COMP deficiency acted via integrin β3 to drive macrophages toward the atherogenic and osteogenic phenotype and thereby aggravate atherosclerotic calcification.
Indexed as
PhenotypeAnimalsAtherosclerosisCartilage Oligomeric Matrix ProteinMacrophagesMiceMice, Inbred C57BLMice, KnockoutVascular CalcificationCartilage Oligomeric Matrix Proteinatherosclerosiscartilage oligomeric matrix proteinextracellular matrixmacrophagesphenotypevascular calcification
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