The adhesion molecule P-selectin and cardiovascular disease

Abstract

The adhesion molecule P-selectin (CD62P) is of interest because of its role in modulating interactions between blood cells and the endothelium, and also because of the possible use of the soluble form as a plasma predictor of adverse cardiovascular events. Although present on the external cell surface of both activated endothelium and activated platelets, it now seems clear that most, if not all, of the measured plasma P-selectin is of platelet origin. P-selectin is partially responsible for the adhesion of certain leukocytes and platelets to the endothelium. Animal models have also shown the important role of P-selectin in the process of atherogenesis. For example, increased P-selectin expression has been demonstrated on active atherosclerotic plaques; in contrast, fibrotic inactive plaques lack P-selectin expression, and animals lacking P-selectin have a decreased tendency to form atherosclerotic plaques. Increased levels of soluble P-selectin in the plasma have also been demonstrated in a variety of cardiovascular disorders, including coronary artery disease, hypertension and atrial fibrillation, with some relationship to prognosis. The objective of this review is to provide an overview of the current literature on this molecule and thus present a concise view of its potential in dissecting the pathophysiology of atherosclerosis. In doing so we shall focus primarily on human biology but will note a small number of excellent lessons provided by non-human work.

Endothelial dysfunction is associated with increased levels of biomarkers in essential hypertension

“…Selectins are markers of endothelial and platelet activation and Endothelial dysfunction and biomarkers A de la Sierra and M Larrousse they both act in the first step of the atherosclerotic process by favouring rolling of leukocytes to the endothelial surface. 28,29 Furthermore, MCP-1 is also responsible for monocyte recruitment and trafficking, and has been found in both human and animal atherosclerotic lesions. 30 They have all been related to the risk of future cardiovascular events in healthy women 31 and especially in patients with coronary artery disease.…”

Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP

“…Most investigators believe the major source of soluble P-selectin is platelets. 13 Many of the cellular effects of thrombin are initiated via activation of a family of protease-activated receptors (PARs), which are coupled to heterotrimeric G-proteins. PARs are unique among G-protein-coupled receptors (GPCRs) in that they are activated by thrombin through proteolytic generation of a tethered ligand.…”

Aspects of bleeding complications and hemostasis at central line insertion and mild induced hypothermia

“…Following platelet activation, -granules exocytose and release the unique Pselectin protein CD62P, which becomes expressed on the platelet surface and can be detected with fluorescent antibodies in the flow cytometry instrument [65].…”