Ziad Mallat is the British Heart Foundation Professor of Cardiovascular Medicine at the University of Cambridge, Addenbrooke’s Hospital, UK. He received his MD and qualification in Cardiovascular Diseases from the University of Pierre et Marie Curie in 1996, and his Ph.D. in Vascular Biology, Thrombosis and Haemostasis from University of Paris-Diderot in 1999. He subsequently joined INSERM, Paris in 1998 as Assistant Research Professor, became Associate Professor in 2002 and Research Professor in 2007. His research aims to understand the role of immune responses in the development and progression of cardiovascular diseases. Professor Mallat was the first to identify a major atheroprotective role of regulatory T cells and associated anti-inflammatory cytokines, IL-10 and TGF-β. More recently, he identified selective pathogenic and protective roles for defined B cell and innate lymphoid cell subsets in atherosclerosis and cardiac remodelling following ischaemic injury. His basic science research is complemented by proof-of-concept clinical trials in patients with coronary artery disease. Professor Mallat is Associate Editor of Arteriosclerosis Thrombosis and Vascular Biology, Atherosclerosis, Consulting Editor for Cardiovascular Research, and serves on the Editorial Board of Circulation Research, and JCI Insight.
Tuesday 02 June 09:00
Immune modulation in atherosclerosis
Atherosclerosis is well recognised as a chronic inflammatory disease of the arterial wall, responsible for most ischaemic cardiovascular events. Moreover, inflammation may account for a substantial proportion of the residual risk for cardiovascular disease that persists in high risk patients on current therapies. Both innate and adaptive immune responses are involved in all stages of atherosclerosis. If adaptive immune responses occur early during the disease process, then despite reduction in risk factors such as low-density lipoprotein (LDL) cholesterol, there may be sustained production of pathogenic effectors.
T cell and B cell responses play prominent roles in atherosclerotic lesion development and inflammation. T cells are found within coronary atherosclerotic plaques at many stages of disease progression. Indeed, various functional T cell subsets have been associated with cardiovascular disease, whereas levels of regulatory T cells, which dampen immune responses in many ways, are reduced. B cells control cellular immune responses through cell-cell contact, antigen presentation, and cytokine production, and thereby participate in systemic and local immune responses in atherosclerotic arteries. To date, both proatherogenic and antiatherogenic properties have been assigned to B cells, depending on subsets and how they are functionally targeted.
Deciphering the role of specific subtypes of immune cells in atherosclerotic plaque development offers the potential for novel and specific therapeutic strategies to limit progression of atherosclerosis and reduce residual cardiovascular risk.
Zhao TX, Mallat Z. Targeting the immune system in atherosclerosis: JACC State-of-the-Art Review. J Am Coll Cardiol 2019;73:1691-706.
Sage AP, Tsiantoulas D, Binder CJ, Mallat Z. The role of B cells in atherosclerosis. Nat Rev Cardiol 2019;16:180-96.
Zhao TX, Kostapanos M, Griffiths C, Arbon EL, Hubsch A, Kaloyirou F, Helmy J, Hoole SP, Rudd JHF, Wood G, Burling K, Bond S, Cheriyan J, Mallat Z. Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes (LILACS): protocol and study rationale for a randomised, double-blind, placebo-controlled, phase I/II clinical trial. BMJ Open 2018;8(9):e022452.