This symposium provides an overview of current research in atherosclerosis and vascular biology at experimental and clinical level. The theme of this year’s meeting was “Inflammation in Cardiovascular Disease, and Immunometabolism”. The symposium was formed of two sessions entitled: 1) Targeting Inflammation in Cardiovascular Disease Prevention and 2) Immunometabolism in Cardiovascular Disease.
In the session 1, Prof Christian Weber showed how immunoligand blotting and surface plasmon resonance can be used to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Moreover, interesting data on the role of a specific variant in atypical chemokine receptor 1 in hemotopoiesis have been presented.
Prof Christoph Binder showed that the B cell activating factor receptor (BAFFR) pathway, which is specifically essential for the survival of conventional B lymphocytes (B-2 cells), is a key driver of coronary heart disease. Deletion or antibody-mediated blockade of BAFFR ablates B-2 cells and decreases experimental atherosclerosis. Anti-BAFF immunotherapy is recently approved for treatment of autoimmune systemic lupus erythematosus and can therefore have important clinical implications in atherosclerosis.
Finally, specific highlights of the topics discussed at the session 1 included the presentation of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) clinical trial by Prof Peter Libby. CANTOS was set up to test the inflammatory hypothesis of atherosclerosis and investigate whether blocking pro-inflammatory cytokine, interleukin-1β (IL-1β), can reduce rates of recurrent heart attack and stroke. The trial randomized more than 10 000 people to either a placebo or one of three doses of canakinumab. Analysis of data showed that the dose used of 150 mg, subcutaneously every 3 months, four times a year, could reduce cardiovascular events to about 15% of primary endpoint or 17% on a broader endpoint. On the other hand, there was also a significant increase in infections as expected. The next step will be to seek regulatory approval for canakinumab for the prevention of recurrent cardiovascular events.
The session 2 on immunometabolism was opened by Prof Luke O’ Neil which showed how an endogenous metabolite, itaconate, is required for the activation of the anti-inflammatory transcription factor Nrf2 by lipopolysaccharide in mouse and human macrophages. 4-octyl itaconate, an itaconate derivative, is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. For the first time, it has been demonstrated that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons.
Dr Carolin Daniel showed data demonstrating that a T cell-specific Stat6/Pten axis links cold exposure or beta3-adrenergic receptor, ADRB3, stimulation with Foxp3+ Treg induction and adipose tissue function. The findings demonstrated a new mechanistic model in which tissue-specific Tregs maintain adipose tissue function.
Finally, the role of the metabolic regulation of macrophages in tissues and has been discussed by Dr Jan Van den Bossch; while Dr Daniel Ketelh showed that the activation of the enzyme indoleamine 2,3-dioxygenase-1 (IDO1), which catalyzes the degradation of tryptophan (Trp) along the kynurenine pathway in artery wall, is atheroprotective.
Based on the plenary sessions and the outcome of the meeting, the Working Group on Atherosclerosis and Vascular Biology have proposed new position papers lead by the Nucleus member Dr Daniel Ketelhuth, in which the Working group will provide an understanding of the mechanisms of the immunometabolism to develop novel therapeutic strategies in atherosclerosis.