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SP0113 Monocyte and Macrophage Dynamics in Atherosclerosis and Plaque Vulnerability
  1. M. De Winther
  1. Medical Biochemistry, Academic Medical Center, Amsterdam, Netherlands

Abstract

Inflammation plays a prominent role in atherosclerosis development and associated cardiovascular disease. Macrophages are key immune cells found in atherosclerotic plaques and critically shape atherosclerotic disease development and clinical outcome. They are one of the most plastic cells of the hematopoietic system. In response to micro-environmental stimuli they adopt different polarization states driving their functional repertoire in tissue homeostasis, host defense and pathology. Whilst several efforts have been made to classify macrophages, the binary M1/M2 classification remains the most used and offers a useful reductionist framework to study and describe their function.

We described the association of macrophage subsets with specific regions in human atherosclerotic plaques. Inflammatory M1 macrophages associated with plaque rupture prone shoulder regions, while M2 macrophages dominated in the adventitia. A main focus of our research interest is on the targeting of macrophage regulation, to allow skewing of their phenotype and improve atherosclerosis outcome.

Epigenetic pathways, including histone modifications, are now emerging as important regulators of immune responses. In recent studies we have been identifying histone-modifying enzymes that are regulated in human atherosclerotic plaque stability and affect macrophage functioning. We could show that modifying the epigenome, by for instance targeting of HDAC3, can be used to beneficially influence the phenotype of macrophages, to allow dampening of atherosclerosis development and stabilize atherosclerotic lesions. Additional enzymes have been identified and are being studied.

Overall, monocytes and macrophages are essential regulators of atherosclerotic plaque development and stability, and approaches targeting the functional repertoire of macrophages may hold novel approaches for future atherosclerosis management.

Disclosure of Interest None declared

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