Evolution and Stabilization of Vulnerable Atherosclerotic Plaques

Inflammation and the Development of Atherosclerosis

“…Atherectomy specimens from patients with ACS show that macrophages are disproportionately concentrated in these areas 5) . Macrophages are known to release proteolytic enzymes, such as interstitial collagenase and gelatinase, which degrade collagen, elastin, and other extracellular matrix proteins, ultimately inducing plaque destabilization [19][20][21][22][23] . Neutrophil infiltration at the inflammatory site also contributes to plaque instability and rupture as these cells release reactive oxygen species (ROS), including superoxide anion and hypochlorous acid derived from myeloperoxidase, resulting in further lipid modification and an increase of proteolytic enzymes 24) .…”

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

“…PMC high adhesive capability to activated endothelial cell is due to increasing integrin activation on monocyte and subsequently, increasing cell adhesion to fibronectin, VCAM-1 and ICAM-1 (Da Costa Martins, 2006). Monocytes transmigrate into the atherosclerotic plaque, and change phenotype, becoming macrophages which express scavenger receptors and digest oxLDL to become foam cells (Libby & Aikawa, 2001). Fig.…”

“…IFN-inhibits smooth muscle cell new collagen synthesis, which is essensial in supporting fibrous caps, thus weakens fibrous cap and promotes rupture-prone plaque (Libby et al, 2010). Smooth muscle cells in the rupture-prone plaque express HLA-DR which is susceptible to IFN-action (Libby & Aikawa, 2001). Furthermore, activated T cells induce production of MMP and tissue factor, mediated by CD40-CD40L binding, which enhances the thrombogenicity of the plaque lipid-rich core (Libby et al, 2010).…”

“…Rupture of fibrous cap lining the plaque is account for 60-65% of occlusive thrombi and erosion of endothelial cells lining the plaque is responsible for the rest 35-40% (Dickson & Gottlieb, 2003). In the rupture-prone atherosclerotic plaque, fibrous cap maintains protective role for the integrity of the plaque and provides a barrier between the thrombogenic material in the necrotic core and circulating blood components, mainly platelets and coagulation factors (Libby & Aikawa, 2001). As plaque progressed, leukocyte-driven inflammation is heightened in the intimal layer.…”

“…As plaque progressed, leukocyte-driven inflammation is heightened in the intimal layer. Inflamed leukocytes can hinder biosynthesis of collagen from smooth muscle cells and can themselves overexpress collagen-degrading proteinases which in turn give the condition of the imbalance between collagen synthesis and degradation, thus weakening the fibrous caps and lead to plaque rupture (Libby & Aikawa, 2001). Furthermore, leukocytes participate in augmentation the production of the procoagulant factor, primarily tissue factor, in plaque lesion and give rise to the high thrombogenicity of the plaque's lipid core (Libby et al, 2010).…”