Defining Novel Regulatory Mechanisms of Macrophage CD36 to Inhibit Atherosclerosis

Project Summary:

Cardiovascular disease, commonly referred to as heart disease, remains the leading cause of death in both the U.S. and Wisconsin. Most forms of the disease that lead to life-threatening conditions such as heart attack or stroke are caused by a pathological condition called atherosclerosis. Atherosclerosis is characterized by lipid-loaded plaques that build up in artery walls, facilitated by chronic inflammation. The scavenger receptor CD36 is highly expressed on the surface of macrophages. CD36-mediated oxidized LDL uptake is responsible for lipid overloading and foam cell formation, the hallmark of atherosclerosis development. The project team also demonstrated that oxLDL/CD36 axis facilitates chronic inflammatory activation in macrophages, which drives the progression of atherosclerosis. This project will investigate and define novel mechanisms by which a mitochondrial-derived molecule called itaconate inhibits atherosclerosis by specifically suppressing the proatherogenic functions of CD36. In vitro and in vivo studies will be conducted to test their hypothesis. Successful completion of this project will provide novel therapeutic strategies against atherosclerosis, which may save millions of lives worldwide as well as Wisconsin residents every year.