Atherosclerosis: Difference between revisions

Chronic shifting of the balance towards extracellular matrix metabolism leads to serious consequences for the plaque integrity. As mentioned earlier, it accelerates inflammatory stimulation or activation of apoptosis pathways and therefore leads to death of smooth muscle and foam cells. Cell death leads to release of cellular contents, whereby more lipids and cellular debris is absorbed to the dynamic lipid core. Due to this process, the size of the lipid core grows and as a result alters biomechanical environment and hence the stability of the plaque. One example of this is a plaque border adjacent to the normal tissue, called shoulder region, which is the main location where the hemodynamic stress is focused. As the size and the protrusion of the plaque in the vessel increase, the hemodynamic stress will also increase around the shoulder region. Furthermore, local accumulation of foam cells and lymphocytes at this site makes the plaque more susceptible to rupture by accelerating degradation of extracellular matrix. However, although shoulder area is considered as the weakest point where the fibrous cap would mostly likely rupture, there have been autopsy studies that showed an equal number of ruptures occurring at the midportion of the fibrous cap. When the fibrous cap is very thick and contains small lipid core, the plaque is called stable plaque and it may reinforce the narrowing of the artery, but on the other hand diminish the susceptibility to rupture. Plaques with thinner fibrous caps are called vulnerable plaques. They are identified by a large necrotic core, rich with lipid, taking about 25% of the plaque area, and a thin fibrous cap of less than 65 µM thickness, which separates the necrotic core from the vessel lumen. Vulnerable plaque is infiltrated by a large amount of macrophages and a smaller amount of T-lymphocytes. It typically lacks smooth muscle cells due to apoptosis. This type of lesion causes less obstruction in the artery, but is more fragile and has higher susceptibility to rupture and trigger thrombosis than a thick fibrous cap. At this stage, plaque hemorrhage can occur due to rupture of vasa vasorum within a plaque. Vasa vasorum is a newly formed vascularization in the plaque due to tissue damage. Due to its fragility it may rupture easily, increasing the risk to form intraplaque hemorrhage. Intraplaque hemorrhage may lead to subsequent rupture of the fibrous cap (Figure 10) or occlusion of the vessel through intramural hematoma. Plaque calcification is another factor that contributes to plaque rupture. It usually occurs in areas of necrosis and elsewhere in the plaque and can eventually lead to higher rigidity of the vessel wall. Calcification is dependent on mineral deposition and resorption by osteoblast-like and osteoclast-like cells in the vessel wall. In conclusion, there are seven important factors associated with plaque ruptures: range of inflammation area, considerable size of lipid core, fibrous cap thinner than 65 µM, apoptosis leading to fewer smooth muscle cells, disrupted balance of proteolytic enzymes and their inhibitors, plaque calcification, and hemorrhage in the plaque. Although it remains difficult to foresee the clinical consequences, progression to a complicated plaque can lead to major cardiovascular diseases, mostly affecting people in their 50s and 60s, although it may also occur among people at an earlier age.<br />