Macrophage Mitochondrial ROS Disruption of Cholesterol Metabolism During Atherosclerosis

Project Description Narrative:

Heart disease has been the leading cause of death in the U.S. and Wisconsin for many years. In 2020, heart disease accounted for 162.2 deaths per 100,000 in Wisconsin’s population, and the death rate for heart disease has increased in the past decade.

This project aims to define a novel molecular mechanism of atherosclerosis, a major pathological process leading to various cardiovascular diseases (CVDs). Decades of intensive research have focused on the characterization of atherosclerotic plaques, leading to the discovery that one of the major components of the plaques is an innate immune cell called a macrophage. Macrophages are important immune cells found in all the major organs, including our blood vessels which provide protection from bacteria and virus infection. However, macrophages are also major contributors to atherosclerosis when high levels of cholesterols accumulate in these cells. This is why people with high blood cholesterol levels, or “bad cholesterol” (LDL), are at higher risk of CVD.

Unfortunately, at the molecular level, it is still not well understood why macrophages abnormally accumulate cholesterol and form plaques in arteries. This knowledge gap has restricted the design of more efficient therapeutic strategies to combat CVD, which may save thousands of lives in Wisconsin and millions worldwide every year.