Effect of a coronary-heart-disease-associated variant of ADAMTS7 on endothelial cell angiogenesis
| Autor: | Mark J. Caulfield, Li Zhang, Xiangyuan Pu, Shu Ye, Kenneth H. Chan, Chuan-ju Liu, Tom R. Webb, Wei Yang, Nilesh J. Samani, Jianhua Zhu, Andrew D. Moore, Qingzhong Xiao |
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| Rok vydání: | 2020 |
| Předmět: |
Proteomics
0301 basic medicine Angiogenesis ADAMTS7 Protein Neovascularization Physiologic 030204 cardiovascular system & hematology Polymorphism Single Nucleotide Thrombospondin 1 Neovascularization Coronary artery disease 03 medical and health sciences 0302 clinical medicine Cell Movement Blocking antibody Human Umbilical Vein Endothelial Cells medicine Humans RNA Small Interfering Tube formation Gene knockdown Chemistry Endothelial Cells medicine.disease Plaque Atherosclerotic Recombinant Proteins Angiogenesis inhibitor Endothelial stem cell 030104 developmental biology Amino Acid Substitution Culture Media Conditioned Gene Knockdown Techniques Cancer research RNA Interference medicine.symptom Cardiology and Cardiovascular Medicine |
| Zdroj: | Atherosclerosis. 296:11-17 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2020.01.015 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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