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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.

PLA2G10 Gene Variants, sPLA2 Activity and Coronary Heart Disease Risk. Guardiola M, Exeter HJ, Perret C, Folkersen L, Van't Hooft F, Eriksson P, Franco-Cereceda A, Paulsson-Berne G, Palmen J, Li KW, Cooper JA, Khaw KT, Mallat Z, Ninio E, Karabina SA, Humphries SE, Boekholdt SM, Holmes MV, Talmud PJ. Circ Cardiovasc Genet. 2015 Jan 12.

AT1 Receptor Antagonism to Reduce Aortic Expansion in Marfan Syndrome: Lost in Translation or in Need of Different Interpretation? Mallat Z, Daugherty A. Arterioscler Thromb Vasc Biol. 2014 Dec 30.

Hematopoietic IKBKE limits the chronicity of inflammasome priming and metaflammation. Patel MN, Bernard WG, Milev NB, Cawthorn WP, Figg N, Hart D, Prieur X, Virtue S, Hegyi K, Bonnafous S, Bailly-Maitre B, Chu Y, Griffin JL, Mallat Z, Considine RV, Tran A, Gual P, Takeuchi O, Akira S, Vidal-Puig A, Bennett MR, Sethi JK. Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):506-11.

Angiotensin II Mobilizes Spleen Monocytes to Promote the Development of Abdominal Aortic Aneurysm in Apoe-/- Mice. Mellak S, Oufella HA, Esposito B, Loyer X, Poirier M, Tedder TF, Tedgui A, Mallat Z, Potteaux S. Arterioscler Thromb Vasc Biol. 2014 Dec 18.

Targeting B Cells in Atherosclerosis: Closing the Gap From Bench to Bedside. Tsiantoulas D, Sage AP, Mallat Z, Binder CJ. Arterioscler Thromb Vasc Biol. 2014 Oct 30.

Reversal of hypoxia in murine atherosclerosis prevents necrotic core expansion by enhancing efferocytosis. Marsch E, Theelen TL, Demandt JA, Jeurissen M, van Gink M, Verjans R, Janssen A, Cleutjens JP, Meex SJ, Donners MM, Haenen GR, Schalkwijk CG, Dubois LJ, Lambin P, Mallat Z, Gijbels MJ, Heemskerk JW, Fisher EA, Biessen EA, Janssen BJ, Daemen MJ, Sluimer JC. Arterioscler Thromb Vasc Biol. 2014 Dec;34(12):2545-53.

IL-17 and Th17 Cells in Atherosclerosis: Subtle and Contextual Roles. Taleb S, Tedgui A, Mallat Z. Arterioscler Thromb Vasc Biol. 2014 Sep 18.

MHC Class II-restricted antigen presentation by plasmacytoid dendritic cells drives proatherogenic T cell immunity. Sage AP, Murphy D, Maffia P, Masters LM, Sabir SR, Baker LL, Cambrook H, Finigan AJ, Ait-Oufella H, Grassia G, Harrison JE, Ludewig B, Reith W, Hansson GK, Reizis B, Hugues S, Mallat Z. Circulation. 2014 Oct 14;130(16):1363-73.

Deletion of chromosome 9p21 noncoding cardiovascular risk interval in mice alters smad2 signaling and promotes vascular aneurysm. Loinard C, Basatemur G, Masters L, Baker L, Harrison J, Figg N, Vilar J, Sage AP, Mallat Z. Circ Cardiovasc Genet. 2014 Dec;7(6):799-805.

MicroRNA-21 coordinates human multipotent cardiovascular progenitors therapeutic potential. Richart A, Loyer X, Néri T, Howangyin K, Guérin CL, Ngkelo A, Bakker W, Zlatanova I, Rouanet M, Vilar J, Lévy B, Rothenberg M, Mallat Z, Pucéat M, Silvestre JS. Stem Cells. 2014 Nov;32(11):2908-22.

Multiple potential roles for B cells in atherosclerosis. Sage AP, Mallat Z. Ann Med. 2014 Aug;46(5):297-303.

Adaptive (T and B cells) immunity and control by dendritic cells in atherosclerosis. Ait-Oufella H, Sage AP, Mallat Z, Tedgui A. Circ Res. 2014 May 9;114(10):1640-60.

The role of the inflammasome in cardiovascular diseases. Li X, Deroide N, Mallat Z. J Mol Med (Berl). 2014 Apr;92(4):307-19.

Novel genetic approach to investigate the role of plasma secretory phospholipase A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian randomization analysis using PLA2G5 expression levels. Holmes MV, Exeter HJ, Folkersen L, Nelson CP, Guardiola M, Cooper JA, Sofat R, Boekholdt SM, Khaw KT, Li KW, Smith AJ, Van't Hooft F, Eriksson P, Franco-Cereceda A, Asselbergs FW, Boer JM, Onland-Moret NC, Hofker M, Erdmann J, Kivimaki M, Kumari M, Reiner AP, Keating BJ, Humphries SE, Hingorani AD, Mallat Z, Samani NJ, Talmud PJ; CARDIoGRAM Consortium. Circ Cardiovasc Genet. 2014 Apr;7(2):144-50.

More publications available through PubMed.

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