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Endothelial overexp...
Endothelial overexpression of LOX-1 increases plaque formation and promotes atherosclerosis in vivo
- Article/chapterEnglish2014
Publisher, publication year, extent ...
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2014-01-12
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Oxford University Press (OUP),2014
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LIBRIS-ID:oai:gup.ub.gu.se/206766
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https://gup.ub.gu.se/publication/206766URI
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https://doi.org/10.1093/eurheartj/eht532DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:129957308URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Aims Lectin-like oxLDL receptor-1 (LOX-1) mediates the uptake of oxidized low-density lipoprotein (oxLDL) in endothelial cells and macrophages. However, the different atherogenic potential of LOX-1-mediated endothelial and macrophage oxLDL uptake remains unclear. The present study was designed to investigate the in vivo role of endothelial LOX-1 in atherogenesis. Methods and results Endothelial-specific LOX-1 transgenic mice were generated using the Tie2 promoter (LOX-1TG). Oxidized low-density lipoprotein uptake was enhanced in cultured endothelial cells, but not in macrophages of LOX-1TG mice. Six-week-old male LOX-1TG and wild-type (WT) mice were fed a high-cholesterol diet (HCD) for 30 weeks. Increased reactive oxygen species production, impaired endothelial nitric oxide synthase activity and endothelial dysfunction were observed in LOX-1TG mice as compared with WT littermates. LOX-1 overexpression led to p38 phosphorylation, increased nuclear factor kappa B activity and subsequent up-regulation of vascular cell adhesion molecule-1, thereby favouring macrophage accumulation and aortic fatty streaks. Consistently, HCD-fed double-mutant LOX-1TG/ApoE(-/-) displayed oxidative stress and vascular inflammation with higher aortic plaques than ApoE(-/-) controls. Finally, bone marrow transplantation experiments showed that endothelial LOX-1 was sufficient for atherosclerosis development in vivo. Conclusions Endothelial-specific LOX-1 overexpression enhanced aortic oxLDL levels, thereby favouring endothelial dysfunction, vascular inflammation and plaque formation. Thus, LOX-1 may serve as a novel therapeutic target for atherosclerosis.
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Rozenberg, I.
(author)
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Paneni, F.Karolinska Institutet
(author)
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Camici, G. G.
(author)
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Shi, Y.
(author)
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Doerries, C.
(author)
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Sledzinska, A.
(author)
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Mocharla, P.
(author)
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Breitenstein, A.
(author)
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Lohmann, C.
(author)
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Stein, S.
(author)
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von Lukowicz, T.
(author)
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Kurrer, M. O.
(author)
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Borén, Jan,1963Gothenburg University,Göteborgs universitet,Center for Cardiovascular and Metabolic Research (CMR)(Swepub:gu)xborej
(author)
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Becher, B.
(author)
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Tanner, F. C.
(author)
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Landmesser, U.
(author)
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Matter, C. M.
(author)
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Luscher, T. F.
(author)
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Karolinska InstitutetCenter for Cardiovascular and Metabolic Research (CMR)
(creator_code:org_t)
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In:European Heart Journal: Oxford University Press (OUP)35:40, s. 2839-28480195-668X1522-9645
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- By the author/editor
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Akhmedov, A.
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Rozenberg, I.
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Paneni, F.
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Camici, G. G.
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Shi, Y.
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Doerries, C.
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show more...
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Sledzinska, A.
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Mocharla, P.
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Breitenstein, A.
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Lohmann, C.
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Stein, S.
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von Lukowicz, T.
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Kurrer, M. O.
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Borén, Jan, 1963
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Becher, B.
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Tanner, F. C.
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Landmesser, U.
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Matter, C. M.
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Luscher, T. F.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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European Heart J ...
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University of Gothenburg
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Karolinska Institutet