Atherosclerosis is the main cause of cardiac diseases witch includes acute myocardial infarction (AMI), unstable angina (UA) and sudden death. Today all these events are known as acute coronary syndrome (ACS). It can ultimately result in clinical presentations ranging from entirely asymptomatic to unstable angina and to massive acute myocardial infarction. ACS is the culmination of a series of events that begins with atherosclerosis, the narrowing of coronary arteries by deposition of highly lipid-filled plaque.
2. chemotaxis of inflammatory cells (particularly monocytes) with foam cell formation;
3. migration and proliferation of smooth muscle cells;
4. accumulation of extracellular matrix and fibrous cap formation;
particles. In the presence of a high LDL-C, the normal LDL-receptor (LDL-R) is repressed and these particles could be taken only by monocytes (scavenges cells) because these type of cells present a LDL-R which is not inhibit by intracellular cholesterol accumulation. These monocytes will enter in the subendothelial space where they will become macrophages with high amounts of cholesterol. These cells, secondary to phagocytosis, will activate the membrane NADPH oxidase which will produce O2- (anion superoxide). O2- will oxidize both circulating and intracellular LDL. They will also secrete chemotactic factors which will attract new monocytes in the arterial vessel.
In the last decade evidence has accumulated that a crucial and causative role in the pathogenesis of atherosclerosis is played by the free radical process known as lipid peroxidation. Free radicals are responsible for the modifications of the LDL apoprotein (apo B100). These particles are known as oxidized LDL (oxLDL) and they are taken only by scavenger receptors of the monocytes. These oxLDL are responsible for many mechanisms involved in atherogenesis such as: the chemotactic effects on other inflammatory cells, endothelial dysfunction, the blockade of macrophage in subendothelial space, stimulation of membrane phospholipase A2 with the releasing of arachidonic acid which is the precursor of prostaglandins and leucotrienes, activation of monocytes/macrophages with cytokines releasing.
2.Chemotaxis of inflammatory cells (particularly monocytes) with foam cell formation. Due to macrophage accumulation in subendothelial space, new monocytes (which contain in specially oxLDL) are attracted. Some of these cells will die and the lipids will abnormal accumulate in the arterial space. They also will stimulate the entrance of new inflammatory cells, in special monocytes and lymphocytes. The macrophages with high amounts of cholesterol are known as foam cells.
3.Migration and proliferation of smooth muscle cells. The inflammatory cells from the subendothelial space will secrete growth factors such PDGF (platelet derived growth factor), MGF(monocyte growth factor ), EGF (epidermal growth factor), which will act on smooth muscle cells from arterial vessel and will stimulate migration of these cells and the proliferation of them in the subendothelial space.
4.Accumulation of extracellular matrix and fibrous cap formation; These smooth muscle cells abnormal proliferate in intima and synthesize connective fibers (as collagen) and other compounds of the extracellular matrix which will form the fibrous cap of the plaque. This plaque will determine either the thickening of the mural and the reduction of the luminal cross-sectional area.
5.Endothelial dysfunction Many authors consider that this mechanism is the first described in the genesis of atherosclerotic plaque. A dysfunctional endothelium will have an increased permeability and thus a higher number of monocytes will pass through the wall into intima. Also these abnormal endothelium cells will secrete adhesion molecules such as VCAM1 which will act as chemotactic factors for other cells like monocytes and lymphocytes. So in the intima of the arterial vessel an inflammatory process will occur.
6.Fibrous cap disruption and thrombus formation Shear stresses from diastolic blood pressure can lead to plaque ruptures in vulnerable areas such as the edges or shoulders of plaque lesions or bifurcations of the arterial tree. The exposure of the core contents of lipids, cellular and extracellular elements (collectively termed \u201cgruel\u201d) results in thrombus formation and platelet aggregation, and the development of chest pain. Incomplete occlusion of the coronary artery leads to unstable angina, while total occlusion lead to acute myocardial infarction (AMI).
The American Heart Association has subdivided the plaque progression into distinct phases. Plaques formed in the early (I-III) are stable in that they have a thick fibrous cap, are not at the risk for rupture, and the patient experiences no cardiac symptoms (fig1). However, for many patients, the plaque progresses to phases IV and V which are lesions characterized by thinning of the cap and are vulnerable to rupture. The fibrous cap can be thinned by inflammation and
monocyte infiltration, activation of metalloproteinases, oxidation of LDL lipoproteins, augmentation of growth factors, and other processes. Shear stress from diastolic blood pressure can lead to plaque rupture in vulnerable areas such as the edges or shoulders of plaque lesions or bifurcations of the arterial tree. The exposure of the core contents of lipids, cellular and extracellular elements (collectively named \u201cgruel\u201d) result in thrombus formation and platelet aggregation, and the development of chest pain. Incomplete occlusion of the coronary artery leads to unstable angina, while total occlusion lead to AMI
\ue000 imaging changes
\ue000 fibrinolytic system activation (spontaneous / therapeutic)
\ue000 increased P-AP2 (plamin \u2013 antiplasmin 2) complexes, fibrin degradation products (D-
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