Abstract
Proteoglycans form a heterogeneous family of proteins with covalently bound sulfated glycosaminoglycans. The extracellular matrix proteoglycan perlecan has been proposed to bind to the platelet- and megakaryocyte-specific receptor G6bB, co-regulating platelet glycoprotein VI (GPVI) signaling. The derived non-sulfate proteoglycan endorepellin was previously shown to enhance platelet adhesion via the collagen receptor, integrin & alpha;2 & beta;1. Here, we compared the roles of perlecan and other matrix proteoglycans in platelet responses and thrombus formation. We used multi-color flow cytometry to measure the degranulation and integrin & alpha;IIb & beta;3 activation of washed platelets in response to various proteoglycans and collagen-related peptide (CRP), the GPVI agonist. Perlecan, but not endorepellin, enhanced the CRP-induced activation of platelets in a time- and concentration-dependent manner. Similar to collagen, immobilized perlecan, but not other proteoglycans, supported static platelet adhesion and spreading. In-flowed whole-blood perlecan diminished shear-dependent platelet adhesion, while it enforced GPVI-dependent thrombus formation-to a larger extent than endorepellin-to induce more contracted aggregates of activated platelets. We concluded that the sulfated proteoglycan perlecan enhances GPVI-dependent platelet responses extending to thrombus formation, but it does so at the expense of reduced adhesion of platelets under flow.
Original language | English |
---|---|
Article number | 13352 |
Number of pages | 13 |
Journal | International Journal of Molecular Sciences |
Volume | 24 |
Issue number | 17 |
DOIs | |
Publication status | Published - 1 Sept 2023 |
Keywords
- collagen-related peptide
- endorepellin
- glycoprotein VI
- perlecan
- platelet spreading
- proteoglycan
- ACUTE CORONARY SYNDROMES
- EXTRACELLULAR-MATRIX
- MECHANISMS
- ADHESION
- RECEPTORS
- PECAM-1
- GPVI