Plaque, Platelets, and Plug – The Pathogenesis of Acute Coronary Syndrome

Acute Coronary Syndromes 78 retention of lipoprotein depends greatly on sustained plasma level of apolipoprotein Bcontaining lipoproteins and, in the lesser degree, lipoprotein size, charge, and composition as well as endothelial permeability (Tabas et al., 2007).Three classes of lipoproteins have apolipoprotein B as integral constituent: very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) (Sniderman et al., 1991).Among them, LDL has the biggest apolipoprotein B proportion and is the most likely to interact with subendothelial proteoglycan (Sniderman et al., 1991).Modification of LDL apolipoprotein B entrapped in intimal layer by oxidative mechanism results in oxidative LDL (oxLDL) (Stocker & Keaney, 2004).Smooth muscle cells, endothelial cells and macrophages are capable to modify LDL via oxidative modification (Diaz et al., 1997).OxLDL is susceptible to scavenging macrophages and gives rise to the generation of cholesterol-laden foam cells (Stocker & Keaney, 2004).OxLDL continuously activates adjacent endothelial cells.Activated endothelial cells express adhesion molecules on their luminal surfaces which attract inflammatory cells from circulation, mainly monocytes and lymphocytes which transmigrate to intimal layer.The blend of inflammatory and resident vascular cells promotes the formation of atherosclerotic plaque.Arterial smooth muscle cells proliferate and migrate to the intimal layer in response to several growth factors releasing from chronic inflammation microenvironment in the intimal layer (Libby, 2002).Smooth muscle cells form a layer which envelopes the core of "inflammatory nidus" at the endothelial site, produce and release collagen and thus shape the so called fibrous cap.Below the cap, "inflammatory nidus" continuously attracts circulating LDL, modifies it and recognizes it as antigen which attracts more inflammatory cells.Atherosclerotic plaque mainly composes of two constructions which undergo dynamic changes: fibrous cap and lipid-rich core.The theories of how plaque originated have been proposed.Response-to-injury theory proposes the initial step in atherogenesis is endothelial denudation due to injurious substance or forces leading to alteration of normal vascular homeostatic properties (Ross, 1993).Injury to endothelial cells enhances endothelial permeability and adhesiveness for leukocytes to attach and migrate into subendothelial.Here inflammation occurs and macrophage recruitment and platelet adhesion and aggregation take place, which promote procoagulant tendency of the plaque.Response-toretention theory suggests LDL retention into subendothelial is the initial event and the prerequisite for plaque to form (Tabas et al., 2007).Endothelial injury does not play important role in this process, since plasma LDL is capable to cross normal endothelial cells through transcytosis mechanism and retains in subendothelial (Simionescu & Simionescu, 1993).Subsequent events are monocyte recruitment and lipid-laden macrophage formation which initiate subendothelial inflammation (Tabas et al., 2007).Oxidative modification theory indicates that to initiate plaque formation, subendothelial LDL should be modified chemically in order to attract macrophages' scavenger receptor and be internalized to form foam cells (Stocker & Keaney, 2004).Native plasma LDL can enter subendothelial and is taken up by resident vascular cells via LDL receptor-mediated endocytosis.This native LDL does not initiate an inflammatory response and is not phagocytosed by monocytes, thus does not induce atherosclerosis (Torzewsky & Lackner, 2006).As the plaque progress, fibrous cap is thinner and turn out to be fragile due to the imbalance of extracellular matrix metabolism, the infiltration of the fibrous cap by macrophages and foam cells, and the calcification process (Burnier et al., 2009).All of these contribute to fibrous cap weakening and lost its protective role.Once fibrous cap lose its integrity, it www.intechopen.com