Inflammation in atherosclerosis: Imaging, biomarkers and novel therapeutic opportunities

The vast majority of cardiovascular-related morbidity and mortality is caused by atherosclerosis. Although many patients with atherosclerosis never develop any symptoms, clinical manifestations can vary between acute life-threatening situations to chronic minor complaints. Over the past decades, inflammatory pathways have emerged as important drivers of atherosclerosis as well as plaque disruption and thrombosis. These relatively novel insights expand the scope of treatment of atherosclerosis beyond the traditional focus on reducing cholesterol levels and arterial stenoses. However, targeting the inflammatory process of atherosclerosis carries the risk of severe complications arising from prolonged immunosuppression since atherosclerotic lesions typically form over the course of years. Therefore, there is a need to identify patients with prone-to-rupture atherosclerotic plaques, who can benefit from relatively short-term anti-inflammatory interventions. This thesis contributes to this effort by investigating existing and novel imaging strategies to quantify and qualify the atherosclerotic plaque (part I) and by investigating circulating biomarkers to estimate the risk for cardiovascular events (part II). Furthermore, selectively increasing the local concentration of immunosuppressive agents in the atherosclerotic plaque could potentially overcome the side-effects of systemic immune depression. Part III of this thesis describes several clinical trials testing anti-inflammatory strategies in patients with CVD. One of those studies tested the feasibility of using liposomal nanoparticles to deliver an anti-inflammatory agent to the atherosclerotic plaque. Given the global research efforts currently being made in this field, the challenge of developing anti-inflammatory treatment strategies for patients with cardiovascular disease will hopefully be fulfilled in the coming decades.