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Neil3-dependent bas...
Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice
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Skarpengland, T (author)
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Holm, S (author)
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Scheffler, K (author)
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Gregersen, I (author)
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Dahl, TB (author)
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Suganthan, R (author)
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Segers, FM (author)
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Ostlie, I (author)
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Otten, JJT (author)
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Luna, L (author)
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- Ketelhuth, DFJ (author)
- Karolinska Institutet
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Lundberg, AM (author)
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Neurauter, CG (author)
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Hildrestrand, G (author)
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Skjelland, M (author)
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Bjorndal, B (author)
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Svardal, AM (author)
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Iversen, PO (author)
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- Hedin, U (author)
- Karolinska Institutet
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Nygard, S (author)
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Olstad, OK (author)
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Krohg-Sorensen, K (author)
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Slupphaug, G (author)
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Eide, L (author)
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Kusnierczyk, A (author)
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Folkersen, L (author)
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Ueland, T (author)
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Berge, RK (author)
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- Hansson, GK (author)
- Karolinska Institutet
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Biessen, EAL (author)
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Halvorsen, B (author)
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Bjoras, M (author)
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Aukrust, P (author)
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(creator_code:org_t)
- 2016-06-22
- 2016
- English.
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28337-
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https://www.nature.c...
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Abstract
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- Increasing evidence suggests that oxidative DNA damage accumulates in atherosclerosis. Recently, we showed that a genetic variant in the human DNA repair enzyme NEIL3 was associated with increased risk of myocardial infarction. Here, we explored the role of Neil3/NEIL3 in atherogenesis by both clinical and experimental approaches. Human carotid plaques revealed increased NEIL3 mRNA expression which significantly correlated with mRNA levels of the macrophage marker CD68. Apoe−/−Neil3−/− mice on high-fat diet showed accelerated plaque formation as compared to Apoe−/− mice, reflecting an atherogenic lipid profile, increased hepatic triglyceride levels and attenuated macrophage cholesterol efflux capacity. Apoe−/−Neil3−/− mice showed marked alterations in several pathways affecting hepatic lipid metabolism, but no genotypic alterations in genome integrity or genome-wide accumulation of oxidative DNA damage. These results suggest a novel role for the DNA glycosylase Neil3 in atherogenesis in balancing lipid metabolism and macrophage function, potentially independently of genome-wide canonical base excision repair of oxidative DNA damage.
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- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Skarpengland, T
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Holm, S
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Scheffler, K
-
Gregersen, I
-
Dahl, TB
-
Suganthan, R
-
show more...
-
Segers, FM
-
Ostlie, I
-
Otten, JJT
-
Luna, L
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Ketelhuth, DFJ
-
Lundberg, AM
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Neurauter, CG
-
Hildrestrand, G
-
Skjelland, M
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Bjorndal, B
-
Svardal, AM
-
Iversen, PO
-
Hedin, U
-
Nygard, S
-
Olstad, OK
-
Krohg-Sorensen, ...
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Slupphaug, G
-
Eide, L
-
Kusnierczyk, A
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Folkersen, L
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Ueland, T
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Berge, RK
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Hansson, GK
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Biessen, EAL
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Halvorsen, B
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Bjoras, M
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Aukrust, P
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show less...
- Articles in the publication
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Scientific repor ...
- By the university
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Karolinska Institutet