Atherosclerosis is one of the leading causes of heart disease and its presence is an important risk factor for events leading to acute myocardial infarction (AMI). In the past, atherosclerosis was described as a cholesterol and lipid storage phenomenon. Now, however, we know it is a more complicated inflammatory process of the arterial vessels; lipid particles and immune cells together lead to pathogenic, inflammatory changes in the vessel wall. Inflammatory cytokines, macrophages, lipids and lipoproteins instigate the creation of foam cells, which are deposited in the vessel wall and lead to narrowing of the artery.
Atherosclerosis begins with damage to the cells that line the blood vessels. These are endothelial cells. Some possible causes of this cell injury are bacterial infection, hyperlipidemia, hypertension, glycosylated products of diabetes, cytokines from adipose tissue, or exposure to toxins such as pollution and second-hand smoke. Monocytes and lymphocytes then adhere to the injured site. Macrophages enter and ingest proteins and, along with modified lipoproteins, create foam cells. An inflammatory milieu results as cytokines and other inflammatory molecules become involved; foam cells and white blood cells begin secreting cytokines and metalloproteinases. Myeloperoxidase is also released by degranulated white blood cells and macrophages. As inflammation and accumulation of these products continues, fatty dots and streaks are formed on the vessel lining and the formation of plaque begins.
As the atherosclerotic process continues, involved cells proliferate forming a complex extracellular matrix and a fibrous cap. If development continues, possibly over decades, the plaque formations are distributed throughout various vessels and they become calcified or collagenized and make the vessel walls rigid. The risk to patients with significant atherosclerosis is that eventually a narrowing of the artery (stenosis) can cause a reduction in oxygen delivery to tissues and plaque rupture can lead to an acute coronary event. It makes sense that in most patients with narrowed arteries, the disease is only revealed in times of cardiac stress (going up stairs, running, or other exercise.) The cardiac tissue may get enough blood supply and oxygen under normal exertion but when more cardiac output is needed the narrow vessel cannot supply the needed oxygen and ischemia results.