Atherosclerosis underlies the majority of cardiovascular diseases. An inflammatory disease, atherosclerotic cardiovascular disease is characterized by atherosclerotic lesions in arterial blood vessel walls. These atherosclerotic lesions develop over decades as immune cells and lipids collect into complex structures.

Atherosclerosis begins with lipid buildup in the artery wall, the breakdown of endothelial cells that line blood vessels, and subsequent inflammatory reactions that recruit immune cells from the blood to the arterial wall. Once in the arterial wall, immune cells can perpetuate inflammation and enlarge lesions. For example, immune cells called monocytes and macrophages produce inflammatory factors that bring more immune cells to the lesion. In advanced lesions, macrophages can either proliferate or become necrotic and die, forming an acellular core as lesions become larger and less stable. Over time, lesions harden and narrow arteries or become unstable and rupture, creating a thrombus (blood clot) that blocks blood flow. Arterial occlusion leads to myocardial infarction (heart attack), ischemic cardiomyopathy, heart failure, stroke, and peripheral arterial disease, which together remain the leading causes of death globally.

Several risk factors exacerbate atherosclerotic lesion growth. Elevated lipid levels, hypertension, diabetes, and obesity can all contribute to cardiovascular disease. While many therapies have been developed to lower lipids, manage diabetes, and control blood pressure, rates of atherosclerosis continue to rise. One reason may be increasingly unhealthy lifestyles. We are beginning to recognize that poor sleep, unhealthy diets, stress, and lack of exercise contribute to atherosclerosis. Indeed, these lifestyle risk factors can increase inflammation and cardiovascular disease. Genetics also play a role in atherosclerosis, and your genome can predispose risk. By better understanding atherosclerosis—its pathology and risk factors—we will be able to develop new personalized and targeted therapeutics.