Inflammation and lipids in vascular disease

Atherosclerosis is the underlying process for most cardiovascular diseases (CVDs) and is characterized by accumulation of cholesterol and activated immune cells in the arterial wall. The clinical presentations of atherosclerosis are diverse and comprise myocardial infarction, stroke, peripheral arterial disease etc. However, it is still largely unknown why different subjects develop atherosclerotic lesions at different sites in the arterial tree. Dyslipidemia and inflammation are well known risk factors for CVD and the interaction between lipid metabolism and inflammatory processes is considered to aggravate the development of atherosclerosis. This project have been designed to address the following core question: Can the interplay between the lipids and inflammation explain the difference in the clinical manifestations of atherosclerosis?    In the first subproject we will evaluate the involvement of vascular cells in the inflammatory process during healthy conditions and during vascular disease. In this settings we will test the impact of lipids as well as inflammatory mediators on different cellular mechanisms involved in the atherosclerotic process. In the second sub-project we will search for biomarkers or biosignatures that can be used for prediction of future myocardial infarction. We will utilize two well-defined cohorts of subjects with CVD and use proteomics to evaluate circulating inflammatory mediators. In addition to new risk-stratification models, this project will also generate new knowledge about inflammatory pathways involved in the development of atherosclerosis. In the third sub-project we will evaluate the plasma lipid profiles and the inflammatory pattern in subjects with peripheral arterial disease, in order to increase the knowledge regarding mechanism involved in peripheral atherosclerosis development. This will be addressed in a population of patient with different degree of peripheral arterial disease. This approach also gives us the opportunity to evaluate how changes in lipid- and inflammatory pattern are related to disease progression. The data obtained in sub-project one, two and three will be transferred to the synergy project were it will be linked together with already existing biochemical parameters, such as lipid profiles, metabolic patterns and genetic markers. Together with the clinical signatures this will be used as a basis for answering the core question.