Target Identification in Neovascularization

Abstract

According the latest factsheets of the world health organization, cardiovascular disease remains a major burden for western society. Due to an aging population and an unhealthy lifestyle, cardiovascular disease morbidity numbers are still increasing. The incidence is especially high amongst patients with vascular occlusive disease, secondary to atherosclerosis. Due to atherosclerotic plaque progression (stenosis or plaque rupture) blood flow to organs downstream of the occlusion is reduced to such extent that organ failure or even death might follow. Consequently, finding novel therapeutic opportunities is still of interest. One possible alternative is the stimulation of new vessel growth also referred to as neovascularization. The two most prominent processes of neovascularization are angiogenesis and arteriogenesis (collateral vessel growth). An inflammatory environment has been shown essential for the growth of new vessels. This explains why previous targets found to stimulate neovascularization were mainly inflammatory mediators. The emphasis of this thesis is put on the search for new targets. First of all, we focused on different aspects of the IL-33/ST2 pathway, a fairly new pathway involved in many inflammatory processes. Secondary we concentrated on the mast cell and its role in intraplaque angiogenesis. Mast cells are particularly known for their role in allergy, but are also implicated in many inflammatory processes, amongst others atherosclerosis