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Functional investig...
Functional investigation of the coronary artery disease gene SVEP1
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-11-13
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Springer Science and Business Media LLC,2020
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:145338697
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http://kipublications.ki.se/Default.aspx?queryparsed=id:145338697URI
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https://doi.org/10.1007/s00395-020-00828-6DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Added entries (persons, corporate bodies, meetings, titles ...)
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Muller, P
(author)
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Sharifi, AM
(author)
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Wobst, J
(author)
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Winter, H
(author)
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Mokry, M
(author)
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Ma, LJ
(author)
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van der Laan, SW
(author)
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Pang, SC
(author)
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Miritsch, B
(author)
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Hinterdobler, J
(author)
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Werner, J
(author)
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Stiller, B
(author)
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Guldener, U
(author)
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Webb, TR
(author)
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Asselbergs, FW
(author)
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Bjorkegren, JLMKarolinska Institutet
(author)
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Maegdefessel, LKarolinska Institutet
(author)
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Schunkert, H
(author)
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Sager, HB
(author)
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Kessler, T
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:Basic research in cardiology: Springer Science and Business Media LLC115:6, s. 67-1435-18030300-8428
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Winkler, MJ
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Muller, P
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Sharifi, AM
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Wobst, J
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Winter, H
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Mokry, M
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Ma, LJ
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van der Laan, SW
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Pang, SC
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Miritsch, B
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Hinterdobler, J
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Werner, J
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Stiller, B
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Guldener, U
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Webb, TR
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Asselbergs, FW
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Bjorkegren, JLM
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Maegdefessel, L
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Schunkert, H
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Sager, HB
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Kessler, T
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Karolinska Institutet