Cardiovascular Medicine

Research

The Division has assembled a collaborative group of cardiovascular investigators who collectively provide expertise in basic, translational and clinical cardiovascular research and who employ cell and molecular biology, in vivo models, genomics, epigenetics, sequencing, biomarker identification and validation, through to novel imaging, diagnostics and experimental medicine studies to improve patient outcomes. Atherosclerosis leading to myocardial infarction (MI) and stroke is the commonest cause of death in the UK. Inflammation, immunity, cell death (apoptosis), and cell senescence in atherosclerotic plaques are major contributors to atherogenesis, plaque rupture and MI. Our research examines the causes and regulation of these processes in atherosclerosis, with a particular focus on smooth muscle and immune regulation of atherosclerosis and aneurysm formation. Dr Sanjay Sinha and Dr Helle Jørgensen are studying smooth muscle cells derived from embryonic and induced pluripotent stem cells as part of the Oxbridge Centre for Cardiovascular Regenerative Medicine Centre, a network of researchers focused on cardiovascular stem cells and development.

The Division’s major clinical research interests include heart failure, the assessment of viability in dysfunctional myocardium, and the utility of transient ischaemia or novel therapeutics to protect the heart from further insults. We have developed metabolic cardioprotection during PCI (both primary emergency and elective intervention), examined the effect of new agents to treat diabetes on cardiac performance in type 2 diabetes, and determined the optimum use of cardiac resynchronisation therapy based on the underlying pathophysiology.  In our vascular imaging programme, led by Dr James Rudd, we are determining whether inflammation, hypoxia and neovascularisation detected by PET/CT and MRI can improve risk prediction, and whether imaging can illustrate the efficacy of anti-atherosclerosis drugs. Professor Bennett’s group are exploring invasive imaging of atherosclerosis using virtual histology intravascular ultrasound (VH-IVUS), and trying to determine whether plaque disruption can be predicted using stress/strain modelling. This work is undertaken in collaboration with physical scientists in the Engineering and Radiology departments of the University as part of the new Cambridge Cardiovascular Strategic Research Initiative.

Khan FZ, Virdee MS, Palmer CR, Pugh PJ, O’Halloran D, Elsik M, Read PA, Begley D, Fynn SP, Dutka DP.  Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial. J Am Coll Cardiol. 2012; 59(17):1509-18.

Cheung C, Bernardo AS, Trotter MW, Pedersen RA, Sinha S. Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.  Nat Biotechnol. 2012 Jan 15;30(2):165-73.

Gorenne I, Kumar S, Gray K, Figg N, Yu H, Mercer J, Bennett MR. Vascular Smooth Muscle Cell Sirtuin 1 protects against DNA damage and inhibits atherosclerosis. Circulation. 2013;127(3):386-96.

Zheng Y, HumphryM, Maguire JJ, Bennett MR, ClarkeMCH. Intracellular IL-1 receptor 2 binding prevents cleavage and activity of IL-1α, controlling necrosis-induced sterile inflammation. Immunity. 2013;38:285-295.

Deroide N, Li X, Lerouet D, Van Vré E, Baker L, Harrison J, Poittevin M, Masters L, Nih L, Margaill I, Iwakura Y, Ryffel B, Pocard M, Tedgui A, Kubis N, Mallat Z. MFGE8 inhibits inflammasome-induced IL-1β production and limits post-ischemic cerebral injury. J Clin Invest. 2013 123(3):1176-81.

Mäki-Petäjä KM, Elkhawad M, Cheriyan J, Joshi FR, Ostör AJK, Hall FC, Rudd, J.H.*, Wilkinson, I. B.*  Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation. 2012 Nov 20;126(21):2473–80.

Rudd JH, Myers KS, Bansilal S, Machac J, Woodward M, Fuster V, Farkouh ME, Fayad ZA.  Relationships among regional arterial inflammation, calcification, risk factors, and biomarkers: a prospective fluorodeoxyglucose positron-emission tomography/computed tomography imaging study.  Circ Cardiovasc Imaging 2009; 2:107-115.

 Mercer J, Cheng KK, Figg N, Gorenne I, Mahmoudi M, Griffin J, Vidal-Puig A, Logan A, Murphy MP, Bennett MR.  DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome.  Circ Res 2010; 107:1021-1031.

 Hoole SP, Heck PM, White PA, Read PA, Khan SN, West NEJ, O’Sullivan M, Dutka DP.  Stunning and cumulative left ventricular dysfunction occurs late after coronary balloon occlusion in humans: Insights from simultaneous coronary and left ventricular hemodynamic assessment.  J Am Coll Cardiol Intv 2010 3:412-8.

 Ait-Oufella H.; Herbin O.; Bouaziz JD, Binder CJ, Uyttenhove C, Laurans L, Taleb S, Van Vre E, Esposito B, Vilar J, Sirvent J, Van Snick J, Tedgui A, Tedder TF, Mallat Z.  B-Cell depletion reduces the development of atherosclerosis in mice.  J Exp Med 2010; 207:1579-1587.

 Jørgensen HF, Terry A, Beretta C, Pereira CF, Leleu M, Chen ZF, Kelly C, Merkenschlager M, Fisher AG.  REST selectively represses a subset of RE1-containing neuronal genes in mouse embryonic stem cells.  Development 2009; 136:715-721.

Legend

VH-IVUS image of an unstable coronary atherosclerotic plaque in cross section (left) or longitudinal section (right).