Causes of atherosclerosis

There are several theories about how atherosclerosis occurs.

Response-to-injury theory

The response-to-injury theory suggests that atherosclerosis develops as a result of repetitive injury to the inner lining of the artery. This injury could be caused by any number of factors, including:

• Physical stress on the artery lining, such as stress caused by high blood pressure.
• A response to an infection within the artery wall.
• Oxidative damage to the artery lining. Oxidative damage refers to injury caused by unstable molecules called free radicals. Free radicals are formed during reactions between oxygen and LDL ("bad" or low-density lipoprotein) cholesterol.
• High cholesterol. Cholesterol is a major part of the plaque that develops in atherosclerosis. People with elevated LDL ("bad") cholesterol levels or low HDL ("good" or high-density lipoprotein) cholesterol levels are known to have increased risk of coronary artery disease and stroke. Lowering cholesterol levels through diet, exercise, and medication clearly reduces these risks, providing strong evidence of the link between cholesterol and atherosclerosis. Exactly why high cholesterol levels promote plaque formation is not clear. Cholesterol is found normally in all cell membranes, but it may alter the physical properties of the blood vessel wall, making it more susceptible to damage. Oxidized LDL cholesterol may cause injury to the blood vessel wall and promote an inflammatory reaction that clogs the artery lining with debris.

Injury may stimulate cells to grow and divide as part of the inflammatory process. This normal, healing response to chronic injury may actually result in the growth of atherosclerotic plaque.

Growth factors

One of the major features of atherosclerosis is the abnormal growth of smooth muscle cells and immune cells in the plaque. Chemical messengers called growth factors cause these cells to grow and divide. A better understanding of the roles of growth factors may eventually lead to treatments that block the development of atherosclerotic plaque.