Vulnerable Plaque

A vulnerable plaque is a high-risk atherosclerotic lesion displaying structural and functional features (eg, the presence of many inflammatory cells, a large necrotic core, and a thin fibrous cap) that render it prone to rupture. Rupture of vulnerable plaque and subsequent arterial thrombosis is the underlying cause of most cardiovascular events, including myocardial infarction and stroke.

Macrophage

Macrophages play an important role in the immune response by removing dead cells and stimulating other immune system cells. In advanced, high-risk atherosclerotic lesions, activated macrophages express a variety of cytokines, chemokines, growth factors, and other biologically active substances (eg, metalloproteinases and reactive oxygen species) that contribute to plaque vulnerability. An extensive inflammatory cell infiltrate—predominantly within and around the necrotic core and fibrous cap regions—is characteristic of vulnerable plaque.

Lp-PLA2

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that may represent a mechanistic link to plaque vulnerability. Lp-PLA2 is bound to LDL-cholesterol in the plasma and within atherosclerotic plaque, where it generates inflammatory mediators—lysophosphatidylcholine (lysoPC) and oxidized nonesterified fatty acids (oxNEFA)—from oxidized LDL-cholesterol.

Lp-PLA2 is present at high levels in ruptured and high-risk human coronary atheroma. In several prospective epidemiology studies, elevated plasma levels of Lp-PLA2 have been associated with an increased risk of cardiovascular events.

Lp-PLA2 should not to be confused with Lp(a), which is an LDL-like particle that is not related to the enzyme Lp-PLA2.

Oxidized Fatty Acids and lysoPC

Oxidized nonesterified fatty acids (oxNEFA) and lysophosphatidylcholine (lysoPC) are products of the enzymatic activity of Lp-PLA2. In experimental settings, lysoPC and oxNEFA contribute to inflammatory cell recruitment, leukocyte activation, and cell death. Collectively, these effects contribute to inflammation within the atherosclerotic plaque and plaque vulnerability.

Necrotic Core

The necrotic core is a region within high-risk atherosclerotic plaque characterized by a large lipid pool, apoptotic cells, and cellular debris. When exposed to the lumen of the artery, the contents of the necrotic core are highly prothrombotic. A large expanding necrotic core is one characteristic of vulnerable plaque.

Fibrous Cap

The fibrous cap is composed primarily of smooth muscle cells and collagen, which develops on the plaque surface, providing a barrier between the internal components of the plaque and the lumen. In stable plaques, a dense fibrous cap helps prevent the necrotic core from spilling its highly prothrombotic contents into the lumen of the artery. Proteolytic enzymes (eg, matrix metalloproteinases) secreted by inflammatory cells within vulnerable plaque contribute to thinning of the fibrous cap, which increases the risk of fissure or rupture. Disruption of the fibrous cap may lead to the formation of a thrombus or total vascular occlusion. A thin fibrous cap is another characteristic of vulnerable plaque.