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.
Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage AP, Guérin C, Vilar J, Caligiuri G, Tsiantoulas D, Laurans L, Dumeau E, Kotti S, Bruneval P, Charo IF, Binder CJ, Danchin N, Tedgui A, Tedder TF, Silvestre JS, Mallat Z. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med. 2013 Oct;19(10):1273-80.
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 postischemic cerebral injury. J Clin Invest. 2013;123:1176-81.
Ait-Oufella H, Herbin O, Bouaziz JD, Binder CJ, Uyttenhove C, Laurans L, Taleb S, Van Vré E, Esposito B, Vilar J, Sirvent J, Van Snick J, Tedgui A, Tedder TF, Mallat Z (2010) B cell depletion reduces the development of atherosclerosis in mice J Exp Med Aug 2; 207(8): 1579-87
Wang Y, Ait-Oufella H, Herbin O, Bonnin P, Ramkhelawon B, Taleb S, Huang J, Offenstadt G, Combadière C, Rénia L, Johnson JL, Tharaux PL, Tedgui A, Mallat Z (2010) TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice J Clin Invest 120: 422-32