Division of BioTherapeutics
Prevention of Unstable Atherosclerosis
The research group headed by Ilze Bot aims to elucidate the mechanisms that underlie atherosclerotic plaque destabilization, which is the key process that leads to acute cardiovascular syndromes such as a myocardial infarction or stroke.
The main focus of this research line is the mast cell, a potent immune cell type, which accumulates in the atherosclerotic plaque during its progression. Activation of the mast cell in the plaque leads to plaque destabilization and importantly, in patients with cardiovascular disease intraplaque mast cell numbers associate with the incidence of cardiovascular events. These data indicate a causal relation between mast cells in the plaque and disease outcome. In my research line, I therefore aim to identify pathways to therapeutically intervene to prevent destabilization of plaques via the mast cell. We do so by aiming to prevent mast cell recruitment to the advanced plaque and by preventing mast cell activation locally in the plaque. Also, we aim to determine the effect of gender on the mast cell in the plaque. In this research line, both preclinical models and human tissue analysis are combined to identify druggable targets to prevent plaque instability.
- Kritikou E., Depuydt M.A.C., Vries M.R. de, Mulder K.E., Govaert A.M., Smit M.D., Duijn J. van, Foks A.C., Wezel A., Smeets H.J., Slütter B., Quax P.H.A., Kuiper J. & Bot I. (2019), Flow Cytometry-Based Characterization of Mast Cells in Human Atherosclerosis, Cells 8(4): 334.
- Kritikou E., Heijden T. van der, Swart M., Duijn J. van, Slütter B., Wezel A., Smeets H.J., Maffia P., Kuiper J. & Bot I. (2019), Hypercholesterolemia Induces a Mast Cell-CD4+ T Cell Interaction in Atherosclerosis, Journal of Immunology 202(5): 1531-1539.
- Indhirajanti S., Daele P.L.A. van, Bos S., Mulder M.T., Bot I. & Lennep J.E.R. van (2018), Systemic mastocytosis associates with cardiovascular events despite lower plasma lipid levels, Atherosclerosis 268: 152-156.
- Tsiantoulas D., Bot I., Ozsvar-Kozma M., Goederle L., Perkmann T., Hartvigsen K., Conrad D.H., Kuiper J., Mallat Z. & Binder C.J. (2017), Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency, CIRCULATION RESEARCH 120(1): 78-84.
- Shi G.P., Bot I. & Kovanen P.T. (2015), Mast cells in human and experimental cardiometabolic diseases, Nature reviews. Cardiology 12: 643-658.