Immune-Vascular Interactions in Atherosclerosis

Cardiovascular disease is the leading cause of death in the world. We have established the importance of chronic inflammation and adaptive immune reactions in atherosclerosis. This has opened avenues to target vascular inflammation in patients suffering from cardiovascular diseases.

The goals of this research project are (i) to elucidate the immunopathogenesis of atherosclerosis and (ii) to adapt this knowledge for cardiovascular medicine.

The following specific aims will be addressed during the forthcoming four years, provided that the project is fully funded:Characterize effects of immune activation on atherosclerosis.Determine molecular epitopes of LDL particles that trigger immune reactions.Identify druggable effector mechanisms to prevent vascular inflammation and improve lipoprotein metabolism.We have constructed a humanized model system of LDL autoimmunity with T-cell receptor transgenic mice, which enables us to perform detailed studies of immune activation and regulation in atherosclerosis.

Substantial effects are observed on atherosclerosis development and lipoprotein metabolism in the model system, but we need to fully clarify the effector mechanisms in order to find targets for development of new prevention, diagnostics and therapy against atherosclerosis.

We will combine studies in mouse models with experiments in cultures of human plaque cells, and validate findings in human tissue samples derived from our carotid endarterectomy biobank.