Choudhury Group: Understanding Inflammatory processes in Atherosclerosis and Acute Myocardial Infarction

Imaging techniques to characterise atherosclerosis and vascular inflammation

The development and application of tools that will (a) provide insights into the pathophysiology of atherosclerosis and its complications; (b) obtain earlier and more refined diagnosis; and (c) quantify the response to therapeutic interventions.

Clinical Science: Using ‘multi-modal’ vascular MRI it has been possible to quantify vascular disease and measure response to specific treatments rapidly and in small numbers of patients (eg Choudhury RP et al, J Am Coll Cardiol, 2016 PMID: 27737744).  Current work focuses on the characterization of atherosclerotic plaque and in particular non-invasive quantification of plaque lipid-rich core using T2 mapping techniques (Chai et al JACC Cardiovasc Imaging. 2016 PMID: 27743954).

Basic science: The laboratory has developed a new class of ligand-conjugated micro-particles of iron oxide for molecular imaging with MRI. Using imaging probes that target specific molecules it has been possible to illuminate pathology in diverse models of disease that include: atherosclerosis and thrombosis, stroke, ischaemia, reperfusion injury and multiple sclerosis (McAteer MA et al ATVB 2012 PMID: 22499989; McAteer et al. Nat Med, 2007 PMID: 17891147). Current work (in collaboration with Prof Ben Davis and Dr Nicola Sibson) is focused on the clinical translation of this molecular imaging platform and on the development of multi-modal imaging particles. (Perez-Balderas et al Nat Commun 2017 PMID: 28198362)

Understanding and manipulating monocyte and macrophage heterogeneity

The laboratory is interested in the role of monocytes in the development of atherosclerosis and their role in acute myocardial infarction. (Ruparelia et al Nat Rev Cardiol. 2017 Review. PMID: 27905474)

Acute Myocardial Infarction and Myocardial Regeneration:  We have shown that monocytes are activated in the blood in acute MI even before reaching the heart and that the patterns of gene expression in peripheral blood monocytes during myocardial injury are conserved between the mouse and humans (Ruparelia et al Eur Heart J 2015 PMID: 25982896). We have more recently focused on the role of endothelial cell-derived extracellular vesicles (EV) in affecting monocyte function in inflammation. These tiny signalling envelopes contain miRNA, mRNA and proteins that can alter the biological function of many cells types including monocytes. We wish to better understand mechanisms of EV signalling in cardiovascular disease and explore avenues that might be amendable to therapeutic intervention.

In Atherosclerosis: We wish to better understand how factors, both genetic and environmental alter monocyte functions, in monocytes reserve such as the spleen, in the peripheral blood en route to injured tissues and within the atherosclerotic plaque. For instance in response to hyperlipidemia, diabetes and in drug interventions (Digby et al Atherosclerosis 2010 PMID: 19781706; Digby et al ATVB 2012 PMID: 22267479; Chai et al PLoS One 2013 PMID: 23658787).  Current work examines aspects of macrophage function in explanted human atherosclerotic plaque using laser capture micro-dissection to obtain specific cell types.

In Metabolic Disease: Prof Choudhury is PI of the Tripartite Immunometabolism Consortium.  This international research programme, which is funded by the NovoNordisk Foundation, brings together scientists from the University of Oxford, The Karolinska Insitute and University of Copenhagen to address the interactions between diabetes / obesity and cardiovascular disease.  Our own work in this area focuses on how and why immune cell function is altered in the context of diabetes.