Atherosclerosis: Difference between revisions

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 ===Extracellular matrix metabolism===
 Metabolic process in extracellular matrix plays a central role in bridging the plaque progression to plaque rupture. Ultimately, this process weakens the fibrous cap, predisposing it to rupture. This process is influenced by the balance of matrix deposition synthesis by smooth muscle cells and degradation by matrix metalloproteinases (MMP), a class of proteolytic enzymes. For example, PDGF and TGF-β stimulate interstitial collagen production, while inflammatory cytokines such as IFN-γ inhibits collagen synthesis. Inflammatory cytokines also weakens the fibrous cap by stimulating local foam cells to secrete MMP that degrades collagen and elastin of the fibrous cap.
+==Plaque disruption==
+===Plaque integrity===
+Chronic shifting of the balance of extracellular matrix metabolism leads to serious consequences to 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. This process increases the size of the lipid core and as a result alters biomechanical environment and hence the stability of the plaque. Plaque border adjacent to the normal tissue is called shoulder region and it’s 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.
+Plaque integrity and its vulnerability to rupture are highly dependent on the net balance of deposition and distribution of the fibrous cap. When the fibrous cap is very thick, 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 and they cause less obstruction in the artery, but are more fragile and have higher susceptibility to rupture and trigger thrombosis. Characteristically, stable plaques have thick fibrous cap with small lipid core, while vulnerable plaques have thin fibrous cap with rich lipid core, extensive macrophage infiltrate and weakening smooth muscle cells. It is difficult to foresee the ‘clinical’ consequences of the plaque.
+===Thrombogenic potential===
+Disruption of the fibrous cap does not always lead to major clinical events such as myocardial infarction and stroke. For example, small non-occlusive thrombi may be reabsorbed into the plaque, continuing the process of smooth cell growth and fibrous deposition. The extent of how occlusive and transient the thrombus will be is largely dependent on the thrombogenic potential of the plaque.
+The counter balancing of coagulation and fibrinolysis determines the probability of a major clinical event due to occlusive thrombosis. Inflammatory stimuli in the plaque environment incite smooth muscle cells, endothelial cells, and foam cells to release tissue factor that initiates the extrinsic coagulation pathway. Inflammatory stimuli also stimulate expression of antifibrinolytics such as plasminogen activator inhibitor-1 and consequently enhance thrombosis. As mentioned earlier, the activated endothelial cells also contribute to thrombosis and coagulation by depositing fibrin at the vascular wall.
+The concept of ‘vulnerable plaque’ has developed into a new concept of ‘vulnerable patient’ as the recent evidence shows that a person’s susceptibility to coagulation and thus vascular events can be influenced by many other factors such as genetics (e.g. procoagulant prothombin gene mutation), coexisting condition (e.g. diabetes), and lifestyle factors (e.g. smoking, obsesity).
+=1.3 Complications of atherosclerosis =
+Developing of atherosclerotic plaques is not homogenous throughout the vasculature. The following anatomical structures are the most common areas where atherosclerosis takes place, starting from the most common region: dorsal section of the abdominal aorta, proximal coronary arteries, the popliteal arteries, descending thoracic aorta, internal carotid arteries, and renal arteries. It is needless to say that the areas perfused by these vessels are most frequently impaired by the consequences of atherosclerosis. Clinically, this can lead to thromboembolism resulting in major cardiovascular diseases such as stroke and myocardial infarction.