The Contribution of Vascular Proteoglycans to Atherothrombosis: Clinical Implications

Figures

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  Figure 1. Atherosclerosis initiation and progression. The early development of atherosclerosis involves the uptake of LDL cholesterol into the intima and the activation of endothelial cells (ECs), leading to an upregulation in adhesion molecules and increased vascular permeability. Monocytes adhere to endothelial adhesion receptors and migrate into the intima, where they differentiate into macrophages. Scavenger receptors present on the surface of macrophages facilitate the uptake of LDL particles resulting in the transition to foam cells. T lymphocytes also migrate into the intima, where they regulate ECs, smooth muscle cells (SMCs), and innate immune cell function. As the plaque progresses, the fibrous cap can weaken and thin through matrix metalloprotease degradation and reduced capacity of SMCs to regenerate the ECM. Apoptosis of SMCs and macrophages results in a necrotic core comprised of cell debris, rich in lipids. Created using BioRender.

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  Figure 2. Schematic diagrams demonstrating the structure, composition, and risk factors associated with plaques phenotypic of (a) plaque rupture and (b) plaque erosion. Created using BioRender.

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  Figure 3. Antiplatelet drugs. Aspirin inhibits cyclo-oxygenase 1 (COX-1), a key enzyme involved in the conversion of arachidonic acid (AA) to thromboxane A2 (TXA2). Clopidogrel, prasugrel, and ticagrelor target the ADP receptor P2Y12 on the platelet surface. Vorapaxar inhibits thrombin protease-activated receptor 1 (PAR1). Abciximab, eptifibatide, and tirofiban inhibit platelet aggregation by blocking GPIIb/IIIa, preventing fibrinogen and von Willebrand factor binding. Glenzocimab and revacept are novel drugs currently in clinical trial, which interfere with GPVI-collagen binding. Created using BioRender.