Abstract
Platelet-adhesive mechanisms play a well-defined role in hemostasis and thrombosis, but evidence continues to emerge for a relevant contribution to other pathophysiological processes, including inflammation, immune-mediated responses to microbial and viral pathogens, and cancer metastasis. Hemostasis and thrombosis are related aspects of the response to vascular injury, but the former protects from bleeding after trauma, while the latter is a disease mechanism. In either situation, adhesive interactions mediated by specific membrane receptors support the initial attachment of single platelets to cellular and extracellular matrix constituents of the vessel wall and tissues. In the subsequent steps of thrombus growth and stabilization, adhesive interactions mediate platelet-to-platelet cohesion (i.e., aggregation) and anchoring to the fibrin clot. A key functional aspect of platelets is their ability to circulate in a quiescent state surveying the integrity of the inner vascular surface, coupled to a prompt reaction wherever alterations are detected. In many respects, therefore, platelet adhesion to vascular wall structures, to one another, or to other blood cells are facets of the same fundamental biological process. The adaptation of platelet-adhesive functions to the effects of blood flow is the main focus of this review.
| Abbreviations | ||
| ECM | = | extracellular matrix |
| VWF | = | von Willebrand factor |
| VWF-A1 | = | A1 domain of VWF |
| GP | = | glycoprotein |
| MMP | = | matrix metalloproteinases |
| MAGP1 | = | microfibril-associated glycoprotein-1 |
| VWF-A3 | = | A3 domain of VWF |
| ADAMTS | = | A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif |
| CD40L | = | CD40 ligand |
| Gas6 | = | Growth arrest-specific gene 6 product |
| PEAR1 | = | platelet endothelial aggregation receptor 1 |
| SLAM | = | signaling lymphocyte activation molecule |
| PPACK | = | D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone dihydrochloride |
| Abbreviations | ||
| ECM | = | extracellular matrix |
| VWF | = | von Willebrand factor |
| VWF-A1 | = | A1 domain of VWF |
| GP | = | glycoprotein |
| MMP | = | matrix metalloproteinases |
| MAGP1 | = | microfibril-associated glycoprotein-1 |
| VWF-A3 | = | A3 domain of VWF |
| ADAMTS | = | A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif |
| CD40L | = | CD40 ligand |
| Gas6 | = | Growth arrest-specific gene 6 product |
| PEAR1 | = | platelet endothelial aggregation receptor 1 |
| SLAM | = | signaling lymphocyte activation molecule |
| PPACK | = | D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone dihydrochloride |
Acknowledgements
We gratefully acknowledge the many contributions that all the colleagues in the Ruggeri laboratory have made to the original work discussed here. The original work by the author referred to in this review was supported by grants from the National Heart Lung and Blood Institute of the National Institutes of Health (HL-78784, HL-31950, HL-42846, and HL-80718).