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Professor Ziad Mallat

Professor Ziad Mallat

BHF Professor of Cardiovascular Medicine


Office Phone: 01223 768678

Research themes

Inflammation:

Research Interests

Immune modulation in atherosclerosis and vascular aneurysms

Atherosclerosis is a chronic inflammatory disease of the arterial wall responsible for most ischaemic cardiovascular diseases and stroke, the most frequent causes of death worldwide. Although not sharing all risk factors for atherosclerosis, abdominal aortic aneurysm (AAA) is also characterised by an inflammatory and destructive remodelling of the vessel wall and is responsible for a significant number of deaths in Western Countries. Both innate and adaptive immune responses have been involved in the initiation and progression of atherosclerosis and AAA. However, there is currently no specific therapeutic strategy targeting the immuno-inflammatory response in atherosclerosis and no medical therapy has been approved for the prevention of progression or rupture of AAA. Deciphering the role of specific subtypes of immune cells would lead to new, potent and specific therapeutic strategies to limit these devastating diseases.

We have recently shown that subpopulations of natural and/or inducible regulatory T (Treg) cells potently inhibit atherosclerotic lesion development and inflammation. We hypothesise that Treg cells and similarly, B cell type regulatory populations, have a broader role in the control of vascular inflammation and may significantly alter atherosclerosis or AAA development and progression. We will study in detail the mechanisms leading to recruitment of the different T and B cell subsets into the injured vessel wall and the pathways by which they modulate vascular inflammation. We will also develop novel immuno-modulatory and vaccination-based strategies to promote protective immune responses in atherosclerosis and AAA, with the aim to radically change the management and treatment of these common and serious vascular diseases.

Keywords

atherosclerosis ; inflammasome ; vascular aneurysms

Key Publications

Most recent publications are listed on PubMed.

Nus M, Sage AP, Lu Y, Masters L, Lam BYH, Newland S, Weller S, Tsiantoulas D, Raffort J, Marcus D, Finigan A, Kitt L, Figg N, Schirmbeck R, Kneilling M, Yeo GSH, Binder CJ, de la Pompa JL, Mallat Z. Marginal zone B cells control the response of follicular helper T cells to a high cholesterol diet. Nat Med 2017; Apr 17. doi: 10.1038/nm.4315. [Epub ahead of print]

Raffort J, Lareyre F, Clement M, Hassen-Khodja R, Chinetti G, Mallat Z. Monocytes and macrophages in abdominal aortic aneurysm. Nat Rev Cardiol 2017; Apr 13. doi: 10.1038/nrcardio.2017.52. [Epub ahead of print] Review

Sage AP, Mallat Z. Readapting the adaptive immune response - therapeutic strategies for atherosclerosis. Br J Pharmacol. 2017 Jan 4. doi: 10.1111/bph.13700. [Epub ahead of print] Review. PMID: 28052311

Joffre J, Potteaux S, Zeboudj L, Loyer X, Boufenzer A, Laurans L, Esposito B, Vandestienne M, de Jager SC, Hénique C, Zlatanova I, Taleb S, Bruneval P, Tedgui A, Mallat Z, Gibot S, Ait-Oufella H. Genetic and Pharmacological Inhibition of TREM-1 Limits the Development of Experimental Atherosclerosis. J Am Coll Cardiol. 2016;68:2776-2793.

Tsiantoulas D, Bot I, Ozsvar-Kozma M, Göderle L, Perkmann T, Hartvigsen K, Conrad DH, Kuiper J, Mallat Z, Binder CJ. Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency. Circ Res. 2017;120:78-84.

Clément M, Basatemur G, Masters L, Baker L, Bruneval P, Iwawaki T, Kneilling M, Yamasaki S, Goodall J, Mallat Z. Necrotic Cell Sensor Clec4e Promotes a Proatherogenic Macrophage Phenotype Through Activation of the Unfolded Protein Response. Circulation. 2016;134:1039-1051.

Mallat Z, Tedgui A, Henrion D. Role of Microvascular Tone and Extracellular Matrix Contraction in the Regulation of Interstitial Fluid: Implications for Aortic Dissection. Arterioscler Thromb Vasc Biol. 2016;36:1742-7.

Howangyin KY, Zlatanova I, Pinto C, Ngkelo A, Cochain C, Rouanet M, Vilar J, Lemitre M, Stockmann C, Fleischmann BK, Mallat Z, Silvestre JS. Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor. Circulation. 2016;133:826-39.

Metghalchi S, Ponnuswamy P, Simon T, Haddad Y, Laurans L, Clément M, Dalloz M, Romain M, Esposito B, Koropoulis V, Lamas B, Paul JL, Cottin Y, Kotti S, Bruneval P, Callebert J, den Ruijter H, Launay JM, Danchin N, Sokol H, Tedgui A, Taleb S, Mallat Z. Indoleamine 2,3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production. Cell Metab. 2015;22:460-71.

Sage AP, Nus M, Baker LL, Finigan AJ, Masters LM, Mallat Z. Regulatory B cell-specific interleukin-10 is dispensable for atherosclerosis development in mice. Arterioscler Thromb Vasc Biol. 2015;35:1770-3.

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