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Cartilage oligomeric matrix protein is an endogenous ß-arrestin-2-selective allosteric modulator of AT1 receptor counteracting vascular injury.
Fu, Yi; Huang, Yaqian; Yang, Zhao; Chen, Yufei; Zheng, Jingang; Mao, Chenfeng; Li, Zhiqing; Liu, Zhixin; Yu, Bing; Li, Tuoyi; Wang, Meili; Xu, Chanjuan; Zhou, Yiwei; Zhao, Guizhen; Jia, Yiting; Guo, Wei; Jia, Xin; Zhang, Tao; Li, Li; Liu, Ziyi; Guo, Shengchao; Ma, Mingliang; Zhang, Heng; Liu, Bo; Du, Junbao; Wang, Wengong; Tang, Chaoshu; Gao, Pei; Xu, Qingbo; Wang, Xian; Liu, Jianfeng; Sun, Jinpeng; Kong, Wei.
Afiliación
  • Fu Y; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Huang Y; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Yang Z; Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.
  • Chen Y; Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, China.
  • Zheng J; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Mao C; Department of Cardiology, China-Japan Friendship Hospital, Beijing, 100029, China.
  • Li Z; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Liu Z; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Yu B; Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, China.
  • Li T; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Wang M; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Xu C; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Zhou Y; College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology; Key Laboratory of Molecular Biophysics, Ministry of Education, Wuhan, Hubei, 430074, China.
  • Zhao G; College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology; Key Laboratory of Molecular Biophysics, Ministry of Education, Wuhan, Hubei, 430074, China.
  • Jia Y; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Guo W; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Jia X; Department of Vascular Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
  • Zhang T; Department of Vascular Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
  • Li L; Department of Vascular Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
  • Liu Z; Department of Pathology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
  • Guo S; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Ma M; Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, China.
  • Zhang H; Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, China.
  • Liu B; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Du J; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Wang W; Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.
  • Tang C; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • Gao P; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Xu Q; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China.
  • Wang X; Cardiovascular Division, The James Black Centre, King's College London, London, SE5 9NU, UK.
  • Liu J; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
  • Sun J; College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology; Key Laboratory of Molecular Biophysics, Ministry of Education, Wuhan, Hubei, 430074, China.
  • Kong W; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China. sunjinpeng@sdu.edu.cn.
Cell Res ; 31(7): 773-790, 2021 07.
Article en En | MEDLINE | ID: mdl-33510386
Compelling evidence has revealed that biased activation of G protein-coupled receptor (GPCR) signaling, including angiotensin II (AngII) receptor type 1 (AT1) signaling, plays pivotal roles in vascular homeostasis and injury, but whether a clinically relevant endogenous biased antagonism of AT1 signaling exists under physiological and pathophysiological conditions has not been clearly elucidated. Here, we show that an extracellular matrix protein, cartilage oligomeric matrix protein (COMP), acts as an endogenous allosteric biased modulator of the AT1 receptor and its deficiency is clinically associated with abdominal aortic aneurysm (AAA) development. COMP directly interacts with the extracellular N-terminus of the AT1 via its EGF domain and inhibits AT1-ß-arrestin-2 signaling, but not Gq or Gi signaling, in a selective manner through allosteric regulation of AT1 intracellular conformational states. COMP deficiency results in activation of AT1a-ß-arrestin-2 signaling and subsequent exclusive AAA formation in response to AngII infusion. AAAs in COMP-/- or ApoE-/- mice are rescued by AT1a or ß-arrestin-2 deficiency, or the application of a peptidomimetic mimicking the AT1-binding motif of COMP. Explorations of the endogenous biased antagonism of AT1 receptor or other GPCRs may reveal novel therapeutic strategies for cardiovascular diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor de Angiotensina Tipo 1 / Lesiones del Sistema Vascular Límite: Animals / Humans Idioma: En Revista: Cell Res Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor de Angiotensina Tipo 1 / Lesiones del Sistema Vascular Límite: Animals / Humans Idioma: En Revista: Cell Res Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido