INTRAPLAQUE ANGIOGENESIS AND THERAPEUTIC TARGETING OF ANGIOGENESIS

In this thesis we have investigated different approaches to block intraplaque angiogenesis in atherosclerosis. Intraplaque angiogenesis is a physiological response to the increased oxygen demand in the plaque but also has adverse effects by facilitating intraplaque hemorrhage and influx of inflammatory mediators, resulting in plaque instability and consequent rupture. To study this phenomenon we used in vitro assays as well as the accelerated atherosclerosis vein graft model in ApoE3*Leiden mice, a unique model in which the formed plaque shows characteristics that highly resemble human atherosclerotic lesions, including intraplaque angiogenesis and hemorrhage and a high inflammatory cell content. We focused on different approaches to restore plaque stability via improving intraplaque oxygen levels as well as via blocking different growth factors signaling. Moreover we studied the effects of our treatments on the interaction between angiogenesis and inflammation both in vitro and in vivo.