Effect of a coronary-heart-disease-associated variant of ADAMTS7 on endothelial cell angiogenesis.
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.
Key words
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