A fibrous cap is a layer of connective tissue that forms over plaques developing within the walls of arteries, acting as a physical barrier covering the plaque’s core. These atheromatous plaques are accumulations of fats, cholesterol, and other substances. The cap itself is a dynamic structure, composed of various cells and proteins. Its presence signifies a particular stage in the development of these arterial lesions.
Formation Within Atherosclerotic Plaque
The development of a fibrous cap is a direct response to atherosclerosis, the gradual buildup of plaque inside arteries. This process starts when the inner lining of an artery, known as the endothelium, becomes damaged. This damage triggers an inflammatory response, causing various cells, including white blood cells, to travel to the site. These cells begin to consume cholesterol, forming what are called foam cells. Over time, these foam cells, along with other cellular debris and lipids, accumulate to form a plaque.
As the plaque grows, the body initiates a process to wall it off from the bloodstream. Smooth muscle cells from the artery wall migrate to the surface of the plaque and produce a matrix that forms this protective layer. This containment strategy is the body’s attempt to stabilize the plaque. The plaque itself can continue to expand underneath this cap, progressively narrowing the channel through which blood can flow.
Biological Composition
The fibrous cap is composed of smooth muscle cells (SMCs) and an extracellular matrix they produce. This matrix is rich in proteins like collagen and elastin, which give the cap its structural integrity and elasticity. Collagen, particularly type I, provides tensile strength that allows the cap to withstand the physical stresses of blood flow. The cap also contains immune cells, such as macrophages and lymphocytes, which influence its stability.
SMCs are the principal cells responsible for synthesizing and maintaining this collagen-rich matrix. After migrating to the plaque, they transition to a synthetic state, focusing on producing the collagen needed to build and repair the cap. The density of these SMCs within the cap is a determinant of its overall robustness.
The Importance of Cap Stability
The stability of an atherosclerotic plaque is determined by the condition of its fibrous cap. A stable plaque has a thick, well-maintained cap rich in collagen and with a high density of smooth muscle cells. This thick barrier sequesters the plaque’s core, making it less likely to rupture under the pressure of blood flow. Stable plaques can narrow arteries but are less prone to causing sudden, acute events.
In contrast, an unstable or “vulnerable” plaque features a thin fibrous cap. A thin cap has fewer smooth muscle cells, a lower collagen content, and a high concentration of inflammatory cells like macrophages. These macrophages release enzymes called matrix metalloproteinases (MMPs), which break down the collagen that gives the cap its strength. This enzymatic degradation progressively weakens and thins the cap, making it fragile.
Chronic inflammation contributes to the transformation of a stable cap into an unstable one. The continuous presence of inflammatory cells within the plaque perpetuates a cycle of matrix degradation. This process often occurs at the “shoulders” of the plaque, the junction where it meets the healthier artery wall. These areas are subjected to high mechanical stress and, when combined with enzymatic weakening, become the most likely points of failure. A cap thinner than 65 micrometers is considered to be at high risk of breaking.
Rupture and Clinical Consequences
The failure of a weakened fibrous cap is known as plaque rupture. When the thin cap breaks, the thrombogenic (clot-promoting) core of the plaque is exposed to the bloodstream. This core is filled with lipids and cellular debris that the body recognizes as a foreign substance, triggering an immediate clotting response. Platelets rush to the site, and a cascade of protein interactions rapidly forms a blood clot, or thrombus.
This newly formed blood clot can grow large enough to completely obstruct the artery at the site of the rupture. If this blockage occurs in one of the coronary arteries that supply blood to the heart muscle, it causes a myocardial infarction, commonly known as a heart attack. The heart muscle is deprived of oxygen and begins to die, leading to severe chest pain and damage to the heart.
A similar event can occur if the ruptured plaque is in an artery leading to the brain, such as the carotid artery. A blood clot forming here can cut off blood flow to a part of the brain, resulting in an ischemic stroke. In some cases, a piece of the thrombus may break off and travel through the bloodstream to lodge in a smaller artery, also causing a stroke. An objective in managing cardiovascular disease is to stabilize vulnerable plaques to prevent the fibrous cap from rupturing.