The Role of IRG1 in Atherosclerosis

Inflammatory vascular diseases like atherosclerosis are a major health concern and one of leading causes of death worldwide especially in higher income populations. Macrophages play an important role in the progression of the disease. They are metabolically dynamic and are continuously shaped by their microenvironment. When they encounter oxidized lipids accumulating into the vessel wall, they become pro-inflammatory cells. During this process they express the immune responsive gene 1 (IRG1) promoting the itaconate production which in turn favors an anti-inflammatory environment. However, the exact metabolic mechanisms linking IRG1 to inflammatory diseases like atherosclerosis are still poorly understood. The project will focus on the effect of IRG1 in the onset and progression of atherosclerosis by doing an in vitro study of metabolism in bone marrow-derived macrophages (BMDMs) of IRG1 deficient mice as well as an in vivo study by comparing the atherosclerotic lesion size of the deficient mice to the wild type mice. A better understanding of underlying mechanisms could guide towards novel players in the treatment of inflammatory atherosclerosis.

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