Loading...
Please wait, while we are loading the content...
Similar Documents
Elastin-derived peptides are new regulators of thrombosis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kawecki, Charlotte Hézard, Nathalie Bocquet, Olivier Poitevin, Gaël Rabenoelina, Fanja Kauskot, Alexandre Duca, Laurent Blaise, Sébastien Romier, Béatrice Martiny, Laurent Nguyen, Philippe Debelle, Laurent Maurice, Pascal |
| Copyright Year | 2014 |
| Abstract | OBJECTIVE Elastin is the major structural extracellular matrix component of the arterial wall that provides the elastic recoil properties and resilience essential for proper vascular function. Elastin-derived peptides (EDP) originating from elastin fragmentation during vascular remodeling have been shown to play an important role in cell physiology and development of cardiovascular diseases. However, their involvement in thrombosis has been unexplored to date. In this study, we investigated the effects of EDP on (1) platelet aggregation and related signaling and (2) thrombus formation. We also characterized the mechanism by which EDP regulate thrombosis. APPROACH AND RESULTS We show that EDP, derived from organo-alkaline hydrolysate of bovine insoluble elastin (kappa-elastin), decrease human platelet aggregation in whole blood induced by weak and strong agonists, such as ADP, epinephrine, arachidonic acid, collagen, TRAP, and U46619. In a mouse whole blood perfusion assay over a collagen matrix, kappa-elastin and VGVAPG, the canonical peptide recognizing the elastin receptor complex, significantly decrease thrombus formation under arterial shear conditions. We confirmed these results in vivo by demonstrating that both kappa-elastin and VGVAPG significantly prolonged the time for complete arteriole occlusion in a mouse model of thrombosis and increased tail bleeding times. Finally, we demonstrate that the regulatory role of EDP on thrombosis relies on platelets that express a functional elastin receptor complex and on the ability of EDP to disrupt plasma von Willebrand factor interaction with collagen. CONCLUSIONS These results highlight the complex nature of the mechanisms governing thrombus formation and reveal an unsuspected regulatory role for circulating EDP in thrombosis. |
| Starting Page | 1810 |
| Ending Page | 1819 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/34/12/2570.full.pdf?download=true |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/early/2014/10/23/ATVBAHA.114.304432.full.pdf |
| PubMed reference number | 25341794v1 |
| Alternate Webpage(s) | https://doi.org/10.1161/ATVBAHA.114.304432 |
| DOI | 10.1161/atvbaha.114.304432 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Volume Number | 34 |
| Issue Number | 12 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenosine Diphosphate Arachidonic Acid Bleeding time procedure Blood Clot Blood Platelet Disorders Blood Platelets Bos taurus Cardiovascular Diseases Cell physiology Epinephrine Extracellular Matrix Hemorrhage Structure of arteriole Thrombosis U-44619 Vascular Remodeling physiological aspects receptor complex valyl-glycyl-valyl-alanyl-prolyl-glycine |
| Content Type | Text |
| Resource Type | Article |
