Disruption of a plaque associated with angina, and myocardial infarction.

The prevalence of healed plaques ranges from 5 to 80%, depending on the vascular bed assessed and clinical presentation.

Atherosclerotic plaques develop over a period of years or decades.

Estimated that as many as 10 asymptomatic plaque disruptions occur for each symptomatic one.

Fibrotic plaques are white and lipid containing plaques are yellow.

Yellow plaques are predictive of disruption and clinical disease.

Thrombotic complications of atherosclerotic disease occurs suddenly and the notion that acute coronary syndrome is developed from a rupture with superficial erosion of an atherosclerotic plaque is it oversimplification of the process that involves plaque activity, blood thrombogenicity, and healing.
Many, if not most, atherosclerotic plaques destabilized without resulting in a classical cardiovascular syndrome.
The occurrence of an acute coronary syndrome probably depends on the disruption of a balance of instability and healing of a plaque.
Acute coronary syndromes have two mechanisms of pathogenesis: Plaque rupture and superficial plaque erosion.
Plaques of all sizes of a ruptured depending upon the stability.
Unstable plaques have a thin overlying, large amounts of cholesterol laden macrophages in the core, and excess inflammatory cytokines.
Once a plaque ruptures, platelets adhere to the thrombotic, ejected plaque material into the artery lumen, leading to obstruction and myocardial infarction.
A plaque disruption activates a proliferative response in the smooth muscles of the plaque, as well as migration of smooth muscle cells from the underlying media to the intima.
Platelet factors promote smooth muscle cell response including the release of TGF-B growth factors and mitogens.
The atherosclerotic plaque core is surrounded by a layer layer of collagen-rich matrix and smooth muscle cells covered by endothelial cells and is described as a fibrous cap.
At the side of plaque healing, smooth muscle cells synthesize an extracellular matrix rich in proteoglycans and type III glycogen.
When plaque healing is complete, type I collagen gradually replaces type III collagen and reepithelialization of the plaque service occurs with creation of a neointima occurs.
Inflammatory cells which are mainly T cells and macrophages infiltrate the plaque and are involved in its progression and thrombosis, leading to an acute coronary syndrome.
The acute stabilization of an atherosclerotic plaque by rupture or erosion leads to thrombosis and an acute coronary syndrome in patients with an impaired healing capacity, a second hit.
In patients with an effective healing system the first hit is contained and the unstable plaque is quieted, and the healing process promotes the development of a more fibrous stable plaque.
it is suggested that plaque healing may protect patients with atherosclerotic disease from the occurrence of acute coronary syndromes, instead leading to a chronic coronary syndrome.
In this present era of lipid lowering therapies, plaque erosion may account for an increasing proportion of acute coronary syndromes.
With repeated cycles of thrombosis and healing areas progressive encroachment of the arterial lumen with stenotic progression possibly leading to coronary artery occlusion in the absence of an acute coronary event.
Statins decrease the yellowness of plaques.
Lipid lowering medication has beneficial effect on plaque healing.
Statins increase the number of intimal smooth muscle cells and expression of procollagen and reduce the proliferation and activation of macrophages, as well as tissue factor expression.
Partial reversal of atherosclerosis has been demonstrated by intravascular ultrasound for the control of major cardiovascular risk factors, including smoking, hypertension, diabetes, and dyslipidemia.
Aggressive lowering of LDL cholesterol stabilizes atherosclerotic plaque that can occur within 30 days of beginning antilipidemic therapy.
The initial plaque reversal can be demonstrated within one or two years thereafter.
Atherosclerotic plaque reversal is based on removal of cholesterol from the plaque in elimination elimination of inflammatory cytokines that lead to plaque rupture.
Coronary and carotid plaque instability have inflammatory link, and progression toward myocardial infarction and stroke is predicted by CRP serum levels.
Atherosclerotic plaque consists of extracellular lipid particles, foam Cells, and debris that has accumulated in the intima of the arterial wall and formed a lipid or necrotic core.

Progression of atherosclerotic plaques in arteries predicted by high sensitivity CRP.Recurrent plaque instability noted by persistent elevations of CRP.

Inflammatory infiltrates found in coronary and carotid plaques of patients who die of acute coronary syndromes or experienced cerebrovascular ischemic events.

Inflammatory markers associated with plaque fragments.

The most frequent causes of thrombosis are plaque rupture and superficial erosion.
Plaque rupture occurs as the fibrous cap covering necrotic core fissures, exposing  highly thrombogenic core to flowing blood.
Atherosclerotic plaque erosion is caused by endothelial damage or denudation and overlying thrombosis in the absence of a frank rupture.
Plaque erosion may involve a first step mediated by local flow perturbation around the plaque in the coronary artery,  which activates the innate immune toll-like receptor 2, leading to endothelial cell death and  desquamation  of the plaque surface area.
A second step is the formation of neutrophil extracellular traps on the denuded endothelial surface which can propagate thrombus formation.
Adaptive immune cells such as CD8 T cells may contribute to erosion.
Plaques subject to erosion usually lack prominent inflammatory infiltrates.
When plaque ruptures or erosion occurs subocclusive or occlusive thrombosis results, causing a symptomatic acute coronary event. 
If thrombosis resistance prevails, thrombus formation is contained and plaque healing occurs.
Atherosclerotic plaque healing occurs after disruption of the plaque and prevents formation of the thrombus, and restores integrity of the blood vessel.
Plaque healing involves circulating blood cells, soluble mediators, local plaque cells and extracellular matrix.
Plaque healing has three phases: thrombus lysis, granulation tissue formation, and vessel re-endothelialization.
With plaque rupture or erosion there is exposure of thrombogenic plaque components-necrotic core, tissue factor, and collagen, providing a stimulus for platelet activation and aggregation and for thrombus formation.
Simultaneously with rupture there is a triggering of endigenous fibrinolysis to physiologically preserve blood vessel patency.
To prevent lasting occlusive thrombus formation requires a functional fibrinolytic system, including the release of tissue plasminogen activator and urokinase plasminogen activator from endothelial cells, the release of elastase and cathepsin G from neutrophils in monocytes trapped in the thrombus directly breaking down fibrin.
Intensive antiplatelet therapy with P2Y12 inhibitors are effective in stabilizing plaque erosion with a progressive reduction in the thrombotic burden at 30 days and complete healing at one year.
Anti-inflammatory therapies such as interleukin –1beta antagonists and low-dose colchicine may reduce the risk of recurrent acute coronary syndrome by improving plaque healing capacity.

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