Maria Belland Olsen‘s PhD research identifies NEIL3 as an important player in prevention of cardiac hypertrophy, as well as scar formation and wound healing following myocardial infarction.
- Mice without the NEIL3-gene have increased mortality and cardiac rupture following a myocardial infarction.
- Mice without NEIL3 are more prone to develop cardiac hypertrophy following pressure overload.
- Conversely, mice with a disturbed lipid profile are less prone to develop hypertrophy if they lack NEIL3.
Thesis: To the Heart of NEIL3 – Experimental studies on NEIL3 DNA glycosylase in cardiac disease
Candidate: Maria Belland Olsen
Time: October 13, 2017 at 12:15
Place: Oslo University Hospital, Rikshospitalet: Blue Auditorium
Link to university website (in Norwegian)
NEIL3 is an enzyme that repairs damaged DNA. Belland Olsen and co-workers have compared mice that lack the NEIL3-gene with normal mice in three different models of cardiovascular disease.
(1) Mice lacking NEIL3 have higher risk of cardiac rupture and subsequent death after myocardial infarction. The study also shows increased expression of the NEIL3-gene in patients with heart failure and in mice following a myocardial infarction.
The increase of Neil3 following myocardial infarction in mice was especially present in a milieu rich on cardiac fibroblast, cells that regulate the process of scarring and wound healing after myocardial infarction. Thus, NEIL3 seems to affect the properties of fibroblasts in a way that offers the best possible scar formation.
(2/3) In mice exposed to pressure overload, the lack of NEIL3 resulted in increased hypertrophy. In mice with a disturbed lipid balance, the opposite was the case: Lack of NEIL3 protected against hypertrophy. NEIL3 is known to initiate DNA repair and thought to be an epigenetic reader. The researchers find altered epigenetic regulation in the mice lacking NEIL3, and suggest that the apparantly divergent results could be due to that NEIL3 modulates the transcriptional response differently in different cardiovascular conditions.
(1) Olsen, M. B., Hildrestrand, G. A., Scheffler, K., Vinge, L. E., Alfsnes, K., Palibrk, V., Wan, J., Neurauter, C. G., Luna, L., Johansen, J., Øgaard, J. D. S., Ohm, I. K., Slupphaug, G., Kuśnierczyk, A., Fiane, A. E., Brorson, S-H., Zhang, L,. Gullestad, L., Louch, W. E., Iversen, P. O., Østlie, I., Klungland, A., Christensen, G., Sjaastad, I., Sætrom, P., Yndestad, A., Aukrust, P., Bjørås, M. & Finsen, A. V. (2017). NEIL3-Dependent Regulation of Cardiac Fibroblast Proliferation Prevents Myocardial Rupture. Cell reports, 18(1), 82-92.
(2/3) To be published.