The heat that hurts  pg. 3

After the study published in Science, “we became more interested in genes related to cholesterol homeostasis—enzymes, proteins, receptors,” he continues. “Recently we’ve expanded that into an interest in inflammation and how macrophages and other cells may play a role in the inflammatory process of atherosclerosis.”

“Living wounds” that will not heal

Atherosclerotic plaques form when blood vessels are injured by chemicals (such as those found in cigarette smoke), high blood pressure or high levels of plasma lipids (fats, like cholesterol).

These plaques are living wounds that can trigger clot formation inside the blood vessel. When a clot forms in an artery that supplies the heart with blood, a heart attack ensues, leading to death of heart muscle. Understanding the cellular and molecular events that lead to atherosclerosis will be critical to making progress against the disease.

Atherosclerotic plaques contain a variety of cell types (see illustration). These include endothelial cells that line the blood vessels and make up the endothelium, and vascular smooth muscle cells that give form and resilience to the blood vessels. Other cells found in plaques, such as pro-inflammatory macrophages and lymphocytes, do not normally reside in the vessel wall. Instead, they remain in the bloodstream and stand ready to mediate inflammatory responses at sites of injury and infection.

As part of the innate immune response system, macrophages are among the first line of defense at sites of injury. Derived from circulating monocytes, these specialized cells engulf and destroy pathogenic organisms and damaged cells. When circulating monocytes encounter injured endothelium, they migrate underneath the endothelium. This invasion of monocytes starts the formation of the atherosclerotic plaque.

Once inside the vessel wall, monocytes differentiate into macrophages that become “activated” and recruit other monocytes and T helper lymphocytes to enter the plaque. They also ingest cholesterol. As macrophages become engorged with cholesterol, they take on a characteristically foamy appearance, and thus are referred to as “foam cells.”

As an atherosclerotic lesion becomes more advanced, an increasing number of foam cells are found in the plaque due to the continual recruitment of macrophages into the lesion. A thin fibrous cap of smooth muscle cells and collagen forms over the plaque, and smooth muscle cells underlying the damaged endothelium begin to proliferate, expanding the volume of the plaque.

Stable atherosclerotic plaques are less likely to cause an acute cardiovascular event such as a heart attack or stroke. Although they restrict blood flow through the lumen of the blood vessel, they rarely cause total occlusion. Instead, plaques provide a site within the vessels where clots can form. Platelets, blood cells involved in clotting, do not attach to the wall of healthy blood vessels. However, they will attach to atherosclerotic lesions.

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