Vulnerable Plaque - Causes

Causes

Researchers have found that accumulation of white blood cells, especially macrophages, termed inflammation, in the walls of the arteries leads to the development of "soft" or vulnerable plaque, which when released aggressively promotes blood clotting.

Researchers now think that vulnerable plaque, (see atherosclerosis) is formed in the following way:

• Lipoprotein LDL particles, which carry fats (including the fat cholesterol) within the water/plasma portion of the blood stream, are absorbed into the artery wall, past the endothelium lining, some of the LDL-lipoprotein particles become oxidized and this attracts macrophages that eat the particles. This process typically starts in childhood. To be specific:
• oxidized lipoprotein particles in the artery wall are an irritant which causes the release of proteins (called cytokines) which attract monocyte white blood cells (white blood cells are the inflammatory cells within the body).
• The cytokines induce the endothelial cells lining the artery wall to display adhesion molecules that attract immune-system white blood cells (to be specific, monocytes).
• The monocytes squeeze into the artery wall. Once inside, they transform into eating cells called macrophages and ingest the oxidized lipoprotein particles.
• The macrophages sometimes become so overloaded with oxidized lipoprotein particles, the cholesterol contained therein and membrane-laden that they are called foam cells. Some of these cells die in place, releasing their fat and cholesterol-laden membranes into the intercellular space. This attracts more macrophages.
• In some regions of increased macrophage activity, macrophage-induced-enzymes erode away the fibrous membrane beneath the endothelium so that the cover separating the plaque from blood flow in the lumen becomes thin and fragile.
• Mechanical stretching and contraction of the artery, with each heart beat, i.e. the pulse, results in rupture of the thin covering membrane, spewing clot-promoting plaque contents into the blood stream.
• The clotting system reacts and forms clots both on the particles shed into the blood stream and locally over the rupture. The clot, if large enough, can block all blood flow. Since all the blood, within seconds, passes through 5-micrometre capillaries, any particles much larger than 5 micrometres block blood flow. (most of the occlusions are too small to see by angiography).
• Most ruptures and clotting events are too small to produce symptoms, though they still produce heart muscle damage, a slow progressive process resulting in ischemic heart disease, the most common basis for congestive heart failure.
• The clot organizes and contracts over time, leaving behind narrowing(s) called stenoses. These narrowing(s) are responsible for the symptoms of the disease and are identified, after the fact, by the changes seen on stress tests and angiography, and treated with bypass surgery and/or angioplasty, with or without stents.

When this inflammation is combined with other stresses, such as high blood pressure (increased mechanical stretching and contraction of the arteries with each heart beat), it can cause the thin covering over the plaque to split, spilling the contents of the vulnerable plaque into the bloodstream. The sticky cytokines on the artery wall capture blood cells (mainly platelets) that accumulate at the site of injury. When these cells clump together, they form a clot, sometimes large enough to block the artery.

The most frequent cause of a cardiac event following rupture of a vulnerable plaque is blood clotting on top of the site of the ruptured plaque that blocks the lumen of the artery, thereby stopping blood flow to the tissues the artery supplies.

Upon rupture, atheroma tissue debris may spill into the blood stream; this debris is often too large (over 5 micrometers) to pass on through the capillaries downstream. In this, the usual situation, the debris obstruct smaller downstream branches of the artery resulting in temporary to permanent end artery/capillary closure with loss of blood supply to, and death of, the previously supplied tissues. A severe case of this can be seen during angioplasty in the slow clearance of injected contrast down the artery lumen. This situation is often termed non-reflow.

In addition, atheroma rupture may allow bleeding from the lumen into the inner tissue of the atheroma, making the atheroma size suddenly increase and protrude into the lumen of the artery, producing lumen narrowing or even total obstruction.