Details

Autor(en) / Beteiligte

• Skarpengland, Tonje
• Holm, Sverre
• Scheffler, Katja
• Gregersen, Ida
• Dahl, Tuva B
• Suganthan, Rajikala
• Segers, Filip M
• Østlie, Ingunn
• Otten, Jeroen J T
• Luna, Luisa
• Ketelhuth, Daniel F J
• Lundberg, Anna M
• Neurauter, Christine G
• Hildrestrand, Gunn
• Skjelland, Mona
• Bjørndal, Bodil
• Svardal, Asbjørn M
• Iversen, Per O
• Hedin, Ulf
• Nygård, Ståle
• Olstad, Ole K
• Krohg-Sørensen, Kirsten
• Slupphaug, Geir
• Eide, Lars
• Kuśnierczyk, Anna
• Folkersen, Lasse
• Ueland, Thor
• Berge, Rolf K
• Hansson, Göran K
• Biessen, Erik A L
• Halvorsen, Bente
• Bjørås, Magnar
• Aukrust, Pål

Titel

Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice

Ist Teil von

• Scientific reports, 2016-06, Vol.6 (1), p.28337-28337, Article 28337

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.