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Cambridge Cardiovascular

 

Research

Mitochondrial dysfunction in atherosclerosis

Atherosclerosis is characterised by fatty plaques in the vessel walls and remains the leading cause of death in the western world. Understanding the underlying mechanisms is key for developing and targeting new treatments.

Mitochondria are the powerhouses of the cell, generating ATP via oxidative phosphorylation to fuel metabolic processes. Mitochondria are also now recognised as critical regulators of inflammation, cell death and proliferation, all processes that determine plaque composition. My work has highlighted that mitochondria are damaged and dysfunctional in atherosclerosis and that this contributes to disease development.

Our work is now focussed on examining what factors regulate mitochondrial function in atherosclerosis and if targeting these pathways has beneficial effects.

Publications

Key publications: 

Foote, K, Reinhold, J, Yu, EPK, Figg, NL, Finigan, A, Murphy, MP, Bennett, MR. Restoring mitochondrial DNA copy number preserves mitochondrial function and delays vascular aging in mice. Aging Cell 2018;17:e12773.

Yu EPK, Reinhold J, Yu H, Starks L, Uryga AK, Foote K, Finigan A, Figg N, Pung YF, Logan A, Murphy MP, Bennett M. Mitochondrial Respiration Is Reduced in Atherosclerosis, Promoting Necrotic Core Formation and Reducing Relative Fibrous Cap Thickness. Arterioscler Thromb Vasc Biol. 2017;37:2322-2332

The role of mitochondrial DNA damage in the development of atherosclerosis. Yu EP, Bennett MR. Free Radic Biol Med. 2016 Nov;100:223-230.

Mitochondrial DNA damage and atherosclerosis. Yu EP, Bennett MR. Trends Endocrinol Metab. 2014 Sep;25(9):481-7.

Mitochondrial DNA damage can promote atherosclerosis independently of reactive oxygen species through effects on smooth muscle cells and monocytes and correlates with higher-risk plaques in humans. Yu E, Calvert PA, Mercer JR, Harrison J, Baker L, Figg NL, Kumar S, Wang JC, Hurst LA, Obaid DR, Logan A, West NE, Clarke MC, Vidal-Puig A, Murphy MP, Bennett MR. Circulation. 2013 Aug 13;128(7):702-12.

Mitochondria in vascular disease. Yu E, Mercer J, Bennett M. Cardiovasc Res. 2012 Jul 15;95(2):173-82.

The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/-/ApoE-/- mice. Mercer JR, Yu E, Figg N, Cheng KK, Prime TA, Griffin JL, Masoodi M, Vidal-Puig A, Murphy MP, Bennett MR. Free Radic Biol Med. 2012 Mar 1;52(5):841-9.

BHF Intermediate Clinical Research Fellow
Honorary Consultant Cardiologist