Atherosclerosis is a progressive condition where plaque accumulates in the arteries, causing them to harden and narrow. The process is a chronic inflammatory disease that develops slowly over many years, often beginning in childhood and worsening with age.
Endothelial Damage The Starting Point
Atherosclerosis begins with injury to the endothelium, the thin layer of cells lining the inside of all arteries. A healthy endothelium maintains the smooth flow of blood and prevents substances from sticking to the artery wall. When this layer is damaged, it loses its protective qualities, becoming more permeable and “sticky,” which sets the stage for plaque to form.
Several factors can inflict this initial injury. High blood pressure exerts a physical force on the artery walls, stressing the endothelial cells. Chemical irritants from tobacco smoke directly harm the delicate lining. Persistently high levels of low-density lipoprotein (LDL) cholesterol, often called “bad” cholesterol, also contribute to endothelial dysfunction.
High blood sugar from diabetes is another cause of endothelial damage. The excess glucose in the blood can lead to chemical changes that impair the function of endothelial cells. These risk factors compromise the integrity of the arterial lining, creating an environment where atherosclerosis can begin.
Formation of Atherosclerotic Plaque
Following damage to the endothelium, the body initiates an inflammatory response. Circulating LDL cholesterol particles then seep through the compromised endothelial layer and accumulate in the artery wall.
The immune system dispatches white blood cells, specifically monocytes, to the site of injury. Once inside the artery wall, these monocytes transform into cells called macrophages. Their primary job is to engulf and remove the trapped LDL cholesterol.
However, macrophages can become overwhelmed by the amount of LDL. As they consume more cholesterol, they transform into “foam cells” because of their lipid-filled, foamy appearance. These foam cells are a hallmark of atherosclerosis.
The accumulation of these foam cells creates the earliest visible sign of the disease, a “fatty streak.” Smooth muscle cells from the deeper layers of the artery wall then migrate toward the surface and multiply. These muscle cells, along with other debris and connective tissue, form a fibrous cap over the foam cells, creating a more defined atherosclerotic plaque.
Plaque Growth and Calcification
Over time, the established plaque continues to grow. It accumulates more lipids, dead cells, and fibrous material, causing it to expand. This growth progressively narrows the lumen, the open channel inside the artery, which restricts blood flow to tissues and organs.
A significant development during this stage is calcification. Calcium deposits begin to form within the plaque, causing it to harden. This process often starts as scattered microcalcifications, which can merge into larger sheets as the plaque matures.
The characteristics of the plaque determine its stability. A “stable” plaque is characterized by a thick fibrous cap that encloses a smaller lipid core and is less prone to breaking apart. In contrast, a “vulnerable” plaque has a thin fibrous cap, a large lipid core, and greater inflammation, making it susceptible to rupture.
Clinical Events From Plaque Rupture
The final and most dangerous stage of atherosclerosis occurs when a plaque becomes unstable and ruptures. The thin fibrous cap of a vulnerable plaque can tear, exposing the clot-promoting material inside its core to the flowing blood. This event is often the trigger for a heart attack or stroke.
The body’s natural response to this rupture is to form a blood clot, or thrombus, at the site. Platelets and other clotting factors rush to the ruptured plaque, building a thrombus on the plaque’s surface. This newly formed clot can grow quickly, sometimes becoming large enough to completely obstruct the already narrowed artery.
The consequences of this blockage depend on the location of the affected artery. If the clot completely blocks a coronary artery, which supplies blood to the heart muscle, it causes a heart attack. If the blockage occurs in an artery that leads to the brain, such as a carotid artery, it results in an ischemic stroke, depriving brain tissue of oxygen.