Search: onr:"swepub:oai:gup.ub.gu.se/206766" >
Endothelial overexp...
Endothelial overexpression of LOX-1 increases plaque formation and promotes atherosclerosis in vivo
-
Akhmedov, A. (author)
-
Rozenberg, I. (author)
-
- Paneni, F. (author)
- Karolinska Institutet
-
show more...
-
Camici, G. G. (author)
-
Shi, Y. (author)
-
Doerries, C. (author)
-
Sledzinska, A. (author)
-
Mocharla, P. (author)
-
Breitenstein, A. (author)
-
Lohmann, C. (author)
-
Stein, S. (author)
-
von Lukowicz, T. (author)
-
Kurrer, M. O. (author)
-
- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Center for Cardiovascular and Metabolic Research (CMR)
-
Becher, B. (author)
-
Tanner, F. C. (author)
-
Landmesser, U. (author)
-
Matter, C. M. (author)
-
Luscher, T. F. (author)
-
show less...
-
(creator_code:org_t)
- 2014-01-12
- 2014
- English.
-
In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:40, s. 2839-2848
- Related links:
-
https://academic.oup...
-
show more...
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- Endothelium
- Vascular inflammation
- Atherosclerosis
- LOW-DENSITY-LIPOPROTEIN
- ADHESION MOLECULE EXPRESSION
- LECTIN-LIKE
- OX-LDL
- MONOCYTE ADHESION
- KNOCKOUT MICE
- CELLS
- RECEPTOR-1
- ATHEROGENESIS
- APOPTOSIS
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Akhmedov, A.
-
Rozenberg, I.
-
Paneni, F.
-
Camici, G. G.
-
Shi, Y.
-
Doerries, C.
-
show more...
-
Sledzinska, A.
-
Mocharla, P.
-
Breitenstein, A.
-
Lohmann, C.
-
Stein, S.
-
von Lukowicz, T.
-
Kurrer, M. O.
-
Borén, Jan, 1963
-
Becher, B.
-
Tanner, F. C.
-
Landmesser, U.
-
Matter, C. M.
-
Luscher, T. F.
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cardiac and Card ...
- Articles in the publication
-
European Heart J ...
- By the university
-
University of Gothenburg
-
Karolinska Institutet