Team Ewa Ehrenborg

Autophagy and cardiovascular disease

The research is about cardiovascular disease, which is a leading cause of morbidity and mortality worldwide. The main culprit is atherosclerosis, which is characterized by accumulation of lipids and connective tissues as well as proliferation of vascular smooth muscle cells in the arteries accompanied by local inflammation. An important control mechanism for the quality of cells and survival in the vessel wall is autophagy, which is a highly conserved self-protecting process as cellular response to stress, in which cellular components are self-consumed and recycled for downstream metabolism.  Autophagy has also been shown to be involved in lipid handling inside the cells and how the inflammatory response is regulated. However, the role of autophagy in the pathogenesis of atherosclerosis in humans is largely unknown.

The overall objective is to identify which factors are of importance for the interplay between lipid metabolism, inflammation and autophagy in cardiovascular disease. We are focusing on how lipid handling in macrophages affects inflammation and autophagy during the atherosclerosis process. We are also aiming at identifying factors/proteins in the autophagy process that are of relevance for the development of vulnerable plaques and/or progression of atherosclerosis in the vessel wall. The objective is to provide new therapeutic approaches to reduce cardiovascular disease.

Group members

• Alice Maestri, Msc, PhD student
• Olivera Werngren, BMA

Research support

• Swedish Research Council
• Swedish Heart-Lung Foundation
• Karolinska Institutet

Key publications

Plaque Evaluation by Ultrasound and Transcriptomics Reveals BCLAF1 as a Regulator of Smooth Muscle Cell Lipid Transdifferentiation in Atherosclerosis.
Rykaczewska U, Zhao Q, Saliba-Gustafsson P, Lengquist M, Kronqvist M, Bergman O, Huang Z, Lund K, Waden K, Pons Vila Z, Caidahl K, Skogsberg J, Vukojevic V, Lindeman JHN, Roy J, Hansson GK, Treuter E, Leeper NJ, Eriksson P, Ehrenborg E, Razuvaev A, Hedin U, Matic L
Arterioscler Thromb Vasc Biol 2022 May;42(5):659-676

Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy.
Saliba-Gustafsson P, Pedrelli M, Gertow K, Werngren O, Janas V, Pourteymour S, Baldassarre D, Tremoli E, Veglia F, Rauramaa R, Smit AJ, Giral P, Kurl S, Pirro M, de Faire U, Humphries SE, Hamsten A, , Gonçalves I, Orho-Melander M, Franco-Cereceda A, Borén J, Eriksson P, Magné J, Parini P, Ehrenborg E
J Intern Med 2019 Dec;286(6):660-675

Cardiac expression of the microsomal triglyceride transport protein protects the heart function during ischemia.
Klevstig M, Arif M, Mannila M, Svedlund S, Mardani I, Ståhlman M, Andersson L, Lindbom M, Miljanovic A, Franco-Cereceda A, Eriksson P, Jeppsson A, Gan LM, Levin M, Mardinoglu A, Ehrenborg E, Borén J
J Mol Cell Cardiol 2019 Dec;137():1-8

Upregulated Autophagy in Calcific Aortic Valve Stenosis Confers Protection of Valvular Interstitial Cells.
Carracedo M, Persson O, Saliba-Gustafsson P, Artiach G, Ehrenborg E, Eriksson P, Franco-Cereceda A, Bäck M
Int J Mol Sci 2019 Mar;20(6):

Deficiency in perilipin 5 reduces mitochondrial function and membrane depolarization in mouse hearts.
Andersson L, Drevinge C, Mardani I, Dalen KT, Ståhlman M, Klevstig M, Lundqvist A, Haugen F, Adiels M, Fogelstrand P, Asin-Cayuela J, Hultén LM, Levin M, Ehrenborg E, Lee YK, Kimmel AR, Borén J, Levin MC
Int J Biochem Cell Biol 2017 Oct;91(Pt A):9-13

Perilipin 5 is protective in the ischemic heart.
Drevinge C, Dalen KT, Mannila MN, Täng MS, Ståhlman M, Klevstig M, Lundqvist A, Mardani I, Haugen F, Fogelstrand P, Adiels M, Asin-Cayuela J, Ekestam C, Gådin JR, Lee YK, Nebb H, Svedlund S, Johansson BR, Hultén LM, Romeo S, Redfors B, Omerovic E, Levin M, Gan LM, Eriksson P, Andersson L, Ehrenborg E, Kimmel AR, Borén J, Levin MC
Int J Cardiol 2016 Sep;219():446-54

ATG16L1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque Vulnerability.
Magné J, Gustafsson P, Jin H, Maegdefessel L, Hultenby K, Wernerson A, Eriksson P, Franco-Cereceda A, Kovanen PT, Gonçalves I, Ehrenborg E
Arterioscler Thromb Vasc Biol 2015 May;35(5):1226-35

The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an α-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans.
Magné J, Aminoff A, Perman Sundelin J, Mannila MN, Gustafsson P, Hultenby K, Wernerson A, Bauer G, Listenberger L, Neville MJ, Karpe F, Borén J, Ehrenborg E
FASEB J 2013 Aug;27(8):3090-9

MicroRNA-9 regulates the expression of peroxisome proliferator-activated receptor δ in human monocytes during the inflammatory response.
Thulin P, Wei T, Werngren O, Cheung L, Fisher RM, Grandér D, Corcoran M, Ehrenborg E
Int J Mol Med 2013 May;31(5):1003-10

Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.
Aminoff A, Ledmyr H, Thulin P, Lundell K, Nunez L, Strandhagen E, Murphy C, Lidberg U, Westerbacka J, Franco-Cereceda A, Liska J, Nielsen LB, Gåfvels M, Mannila MN, Hamsten A, Yki-Järvinen H, Thelle D, Eriksson P, Borén J, Ehrenborg E
J Lipid Res 2010 Jan;51(1):103-11