Inhibition of heteromeric receptor-receptor interactions and its influence on mononuclear phagocyte recruitment in atherosclerosis (Project Lead: Michel Gramberg)

Atherosclerosis and its most significant clinical manifestations, myocardial infarction and stroke, represent a leading cause of death worldwide. Atherosclerosis is characterized by chronic lipid accumulation and inflammatory processes in the tunica intima. Many blood cells such as platelets and mononuclear phagocytes (monocytes, macrophages, and dendritic cells) are involved in these inflammatory processes and in the further development of an atherosclerotic plaque.

Recruitment, activation, and other interactions with mononuclear phagocytes are largely mediated through heterotypic cell-cell interactions. Understanding these complex relationships is essential for elucidating atherosclerosis and could enable new approaches to treatment.

In this project, we focus on the influence of the interplay between platelets and monocytes on the initiation and progression of atherosclerosis. Our emphasis is on specific heteromeric receptor interactions and their impact as well as their inhibition in various in silico, in vitro, and in vivo model systems. Inhibition is performed via macrocycle peptides and aptamers developed for this project.