Your browser doesn't support javascript.
loading
Shift of Macrophage Phenotype Due to Cartilage Oligomeric Matrix Protein Deficiency Drives Atherosclerotic Calcification.
Fu, Yi; Gao, Cheng; Liang, Ying; Wang, Meili; Huang, Yaqian; Ma, Wei; Li, Tuoyi; Jia, Yiting; Yu, Fang; Zhu, Wanlin; Cui, Qinghua; Li, Yanhui; Xu, Qingbo; Wang, Xian; Kong, Wei.
Afiliação
  • Fu Y; From 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 Laborator
  • Gao C; From 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 Laborator
  • Liang Y; From 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 Laborator
  • Wang M; From 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 Laborator
  • Huang Y; From 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 Laborator
  • Ma W; From 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 Laborator
  • Li T; From 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 Laborator
  • Jia Y; From 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 Laborator
  • Yu F; From 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 Laborator
  • Zhu W; From 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 Laborator
  • Cui Q; From 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 Laborator
  • Li Y; From 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 Laborator
  • Xu Q; From 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 Laborator
  • Wang X; From 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 Laborator
  • Kong W; From 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 Laborator
Circ Res ; 119(2): 261-76, 2016 07 08.
Article em En | MEDLINE | ID: mdl-27151399
RATIONALE: Intimal 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. OBJECTIVE: To investigate whether COMP affects atherosclerotic calcification. METHODS AND RESULTS: ApoE(-/-)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 ß3 protein was attenuated in COMP(-/-) macrophages, and overexpression of integrin ß3 inhibited the shift of macrophage phenotypes by COMP deficiency. Furthermore, adeno-associated virus 2-integrin ß3 infection attenuated atherosclerotic calcification in ApoE(-/-)COMP(-/-) mice. Mechanistically, COMP bound directly to ß-tail domain of integrin ß3 via its C-terminus, and blocking of the COMP-integrin ß3 association by ß-tail domain mimicked the COMP deficiency-induced shift in macrophage phenotypes. Similar to COMP deficiency in mice, transduction of adeno-associated virus 2-ß-tail domain enhanced atherosclerotic calcification in ApoE(-/-) mice. CONCLUSIONS: These results reveal that COMP deficiency acted via integrin ß3 to drive macrophages toward the atherogenic and osteogenic phenotype and thereby aggravate atherosclerotic calcification.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenótipo / Aterosclerose / Calcificação Vascular / Proteína de Matriz Oligomérica de Cartilagem / Macrófagos Limite: Animals Idioma: En Revista: Circ Res Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenótipo / Aterosclerose / Calcificação Vascular / Proteína de Matriz Oligomérica de Cartilagem / Macrófagos Limite: Animals Idioma: En Revista: Circ Res Ano de publicação: 2016 Tipo de documento: Article