Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice
| Autor: | Lars Eide, Magnar Bjørås, Kirsten Krohg-Sørensen, Göran K. Hansson, Lasse Folkersen, Daniel F. J. Ketelhuth, Rolf K. Berge, Ingunn Østlie, Bodil Bjørndal, Ulf Hedin, Jeroen J. T. Otten, Tuva B. Dahl, Erik A.L. Biessen, Rajikala Suganthan, Gunn A. Hildrestrand, Per Ole Iversen, Geir Slupphaug, Thor Ueland, Katja Scheffler, Sverre Holm, Asbjørn Svardal, Tonje Skarpengland, Anna Kuśnierczyk, Pål Aukrust, Ole Kristoffer Olstad, Anna M. Lundberg, Christine G. Neurauter, Ståle Nygård, Mona Skjelland, Ida Gregersen, Luisa Luna, Bente Halvorsen, Filip M. Segers |
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| Přispěvatelé: | Promovendi CD, Pathologie, RS: CARIM - R3.06 - The vulnerable plaque: makers and markers |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Apolipoprotein E medicine.medical_specialty DNA Repair Mice Knockout ApoE DNA damage DNA repair Antigens Differentiation Myelomonocytic Biology medicine.disease_cause Article Mice 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being Antigens CD Internal medicine medicine Animals N-Glycosyl Hydrolases Base excision repair Endodeoxyribonucleases Multidisciplinary medicine.diagnostic_test Macrophages Lipid metabolism Atherosclerosis Lipid Metabolism Cardiovascular biology Disease Models Animal Oxidative Stress Cardiovascular diseases 030104 developmental biology Endocrinology Biochemistry DNA glycosylase Lipid profile 030217 neurology & neurosurgery Oxidative stress DNA Damage |
| Zdroj: | Scientific Reports Skarpengland, T, Holm, S, Scheffler, K, Gregersen, I, Dahl, T B, Suganthan, R, Segers, F M, Østlie, I, Otten, J J T, Luna, L, Ketelhuth, D F J, Lundberg, A M, Neurauter, C G, Hildrestrand, G, Skjelland, M, Bjørndal, B, Svardal, A M, Iversen, P O, Hedin, U, Nygård, S, Olstad, O K, Krohg-Sorensen, K, Slupphaug, G, Eide, L, Kusnierczyk, A, Folkersen, L, Ueland, T, Berge, R K, Hansson, G K, Biessen, E A L, Halvorsen, B, Bjørås, M & Aukrust, P 2016, ' Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice ', Scientific Reports, vol. 6, 28337 . https://doi.org/10.1038/srep28337 Scientific Reports, 6:28337. Nature Publishing Group 6:28337 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep28337 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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