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Thrombin, Inflammation, and Cardiovascular Disease: Thrombin

Thrombin, Inflammation, and Cardiovascular Disease: ThrombinThe precipitating cause is less apparent in these cases, and one may speculate that transient platelet aggregation at the site of lesion fracture or erosion, which may be tolerated if occurring in younger hearts, may prove fatal in older, weaker hearts. The atherosclerotic burden associated with events later in life is much greater than that associated with events in younger people, where the actual plaque burden may be limited. comments
This raises the question of whether thrombin might participate in atherosclerotic heart disease in ways that do not directly involve thrombus formation. The answer is that thrombin generation has numerous possible non-thrombotic associations with atherosclerosis and heart disease, and more pathways are certain to be identified. Many of these pathways are discussed in more detail in other sections of this article. Some center on the role of thrombin as a signaling molecule, through thrombin receptors (protease-activated receptors [PARs]). As discussed by Dr. Brass elsewhere in this supplement and by Patterson et al in a review article, these signaling events concern virtually all aspects of vascular biology, including vessel tone, cellular differential, migration and proliferation (especially smooth-muscle cells), angiogenesis and vascular development, and vascular pathology such as atherosclerosis. At least three PARs are expressed by human cells, with attendant G protein-coupled signaling cascades and physiologic effects. Thrombin plays a central role in the activation of all three PARs. Moreover, these signaling events can coordinate with other receptor-based intracellular signaling to modify the resulting effect. In total, then, the possible effects of thrombin in vascular wall biology are large in number and key to both normal and pathologic vascular physiology.