Inhibition of Mast cell Activation in AtheroScleroTic lesions using an Anti-IgE antibody approach (MAST)

Background: Destabilization and subsequent rupture of atherosclerotic plaque is a crucial underlying mechanism of ischemic cardiovascular events. After the activation of mast cells, various cytokines and proteases such as tryptase and chymase are released which contribute to the progression and destabilization of atherosclerotic plaque. This occurs due to the accumulation of lipids, the influx of pro-inflammatory immune cells, apoptosis of macrophages, endothelial cells and smooth muscle cells, matrix degradation and the occurrence of intraplaque hemorrhage. Mast cells accumulate during the progression of atherosclerosis. The number of mast cells in atherosclerotic plaque is associated with an increase in the microvessel density and intraplaque hemorrhage, moreover the number of mast cells are associated with future cardiovascular events. Mast cells can be activated by various stimuli, of which crosslinking of the FcεRI with IgE-antigen complexes is most prominent. Recent animal studies have demonstrated that treatment with anti-IgE can inhibit mast cell activation and effectively reduce plaque size.

Aim: Does single treatment with an anti-IgE monoclonal antibody (omalizumab) affect the degree of mast cell activation in atherosclerotic plaques?

Method: Patients with (a)symptomatic carotid stenosis which will undergo a carotid endarterectomy will be treated with the study medication (omalizumab or placebo) prior to surgery. The study medication will be administrated with subcutaneous injections. During the surgery the plaque will be collected. With the use of flowcytometry the primary endpoint, the degree of mast cell activation, will be determined. Furthermore, individual subsets of other immune cells will be studied with the use of flowcytometry and mast cell activation markers will be determined in blood and atherosclerotic plaque samples.

Hypothesis: We assume that single treatment with an anti-IgE monoclonal antibody can inhibit the degree of mast cell activation in atherosclerotic plaque. In the future, further research will have to show whether the inhibition of mast cell activation is a potential new therapy to prevent atherosclerotic plaque destabilization and ultimately acute cardiovascular events.

We assume that single treatment with an anti-IgE monoclonal antibody can inhibit the degree of mast cell activation in atherosclerotic plaque

Screening, day 0, day 3 and 3 months

Single treatment with Omalizumab 600mg s.c. or placebo