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Effect of a coronary-heart-disease-associated variant of ADAMTS7 on endothelial cell angiogenesis.
Pu, Xiangyuan; Chan, Kenneth; Yang, Wei; Xiao, Qingzhong; Zhang, Li; Moore, Andrew D; Liu, Chuanju; Webb, Tom R; Caulfield, Mark J; Samani, Nilesh J; Zhu, Jianhua; Ye, Shu.
Affiliation
  • Pu X; First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Chan K; William Harvey Research Institute, Queen Mary University of London, London, UK; Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Yang W; Shantou University Medical College, Shantou, China.
  • Xiao Q; William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Zhang L; First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  • Moore AD; William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Liu C; Musculoskeletal Research Center, New York University School of Medicine, New York, NY, USA.
  • Webb TR; Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.
  • Caulfield MJ; William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Samani NJ; Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.
  • Zhu J; First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  • Ye S; Shantou University Medical College, Shantou, China; Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. Electronic address: s_ye@stu.edu.cn.
Atherosclerosis ; 296: 11-17, 2020 03.
Article in En | MEDLINE | ID: mdl-32005000
BACKGROUND AND AIMS: Recent studies have unveiled an association between ADAMTS7 gene variation and coronary artery disease (CAD) caused by atherosclerosis. We investigated if the ADAMTS7 Serine214-to-Proline substitution arising from a CAD-associated variant affected angiogenesis, since neovascularization plays an important role in atherosclerosis. METHODS AND RESULTS: ADAMTS7 knockdown in vascular endothelial cells (ECs) attenuated their angiogenesis potential, whereas augmented ADAMTS7-Ser214 expression had the opposite effect, leading to increased ECs migratory and tube formation ability. Proteomics analysis showed an increase in thrombospondin-1, a reported angiogenesis inhibitor, in culture media conditioned by ECs with ADAMTS7 knockdown and a decrease of thrombospondin-1 in media conditioned by ECs with ADAMTS7-Ser214 overexpression. Cleavage assay indicated that ADAMTS7 possessed thrombospondin-1 degrading activity, which was reduced by the Ser214-to-Pro substitution. The pro-angiogenic effect of ADAMTS7-Ser214 diminished in the presence of a thrombospondin-1 blocking antibody. CONCLUSIONS: The ADAMTS7 Ser217-to-Pro substitution as a result of ADAMTS7 polymorphism affects thrombospondin-1 degradation, thereby promoting atherogenesis through increased EC migration and tube formation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neovascularization, Physiologic / Thrombospondin 1 / Polymorphism, Single Nucleotide / Endothelial Cells Type of study: Risk_factors_studies Limits: Humans Language: En Journal: Atherosclerosis Year: 2020 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neovascularization, Physiologic / Thrombospondin 1 / Polymorphism, Single Nucleotide / Endothelial Cells Type of study: Risk_factors_studies Limits: Humans Language: En Journal: Atherosclerosis Year: 2020 Document type: Article