Functional investigation of the coronary artery disease gene SVEP1.
Basic Res Cardiol
; 115(6): 67, 2020 11 13.
Article
en En
| MEDLINE
| ID: mdl-33185739
ABSTRACT
A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE-/-Svep1+/-) compared to Svep1 wild-type mice (ApoE-/-Svep1+/+) and ApoE-/-Svep1+/- mice displayed elevated plaque neutrophil, Ly6Chigh monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE-/-Svep1+/- mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE-/-Svep1+/- mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de la Arteria Coronaria
/
Proteínas de Unión al Calcio
/
Proteínas
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Moléculas de Adhesión Celular
/
Vasos Coronarios
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Basic Res Cardiol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania