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Vascular PG-M/versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation

Mazzucato, M; Cozzi, M R; Pradella, P; Perissinotto, D; Malmström, Anders LU ; Mörgelin, Matthias LU ; Spessotto, P; Colombatti, A; De Marco, L and Perris, R (2002) In FASEB Journal 16(14). p.1903-1916
Abstract
We have identified a novel von Willebrand factor/fibrinogen/selectin-independent, platelet adhesion-promoting function of vascular PG-M/versicans that may be relevant in normal venous thrombosis and critical in atherosclerotic conditions. A purification scheme was devised to obtain vascular versicans, which by biochemical, immunochemical, and ultrastructural means were asserted to be 1) composed primarily of isoforms V1 and V2; 2) free of contaminants; 3) prevalently substituted with chondroitin-4-sulfate and dermatan sulfate (DS) chains; and 4) capable of binding hyaluronan to form link protein-stabilized ternary complexes. Real-time analysis of human platelet perfused under diverse shear forces showed that they largely failed to bind to... (More)
We have identified a novel von Willebrand factor/fibrinogen/selectin-independent, platelet adhesion-promoting function of vascular PG-M/versicans that may be relevant in normal venous thrombosis and critical in atherosclerotic conditions. A purification scheme was devised to obtain vascular versicans, which by biochemical, immunochemical, and ultrastructural means were asserted to be 1) composed primarily of isoforms V1 and V2; 2) free of contaminants; 3) prevalently substituted with chondroitin-4-sulfate and dermatan sulfate (DS) chains; and 4) capable of binding hyaluronan to form link protein-stabilized ternary complexes. Real-time analysis of human platelet perfused under diverse shear forces showed that they largely failed to bind to several vascular and nonvascular proteoglycans (PGs). In contrast, they bound in a dose- and shear rate-dependent manner to vascular versicans, exhibiting a unique attachment-detachment kinetics and establishing a firm substrate tethering characterized with no significant aggregation. Digestion of these PGs with lyases and competition experiments with purified glycosaminoglycans revealed that platelet adhesion to vascular versicans was primarily mediated by their DS chains. Incorporation of the versicans into fibrillar collagen substrates augmented their adhesive activity and strongly promoted platelet aggregation at low and high shear rates. Affinity chromatography of platelet surfaces on DS columns identified a 120-140 kDa polypeptide complex that behaved as a specific vascular versican binding membrane ligand in solid-phase binding assays. These findings indicate that selective versican variants of the subendothelium may serve as ancillary GPIbalpha/integrin/selectin-independent platelet ligands in healthy and diseased vascular beds and may be directly responsible for the platelet accruing after rupture of atherosclerotic plaques., versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hemostasis, shear stress, proteoglycan
in
FASEB Journal
volume
16
issue
14
pages
1903 - 1916
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • wos:000180574300011
  • pmid:12468455
  • scopus:0036904251
ISSN
1530-6860
language
English
LU publication?
yes
id
c5d254a2-e256-454a-b623-3e1d29231e53 (old id 319538)
alternative location
http://www.fasebj.org.ludwig.lub.lu.se/cgi/reprint/16/14/1903
date added to LUP
2007-11-02 11:39:17
date last changed
2017-01-01 07:02:12
@article{c5d254a2-e256-454a-b623-3e1d29231e53,
  abstract     = {We have identified a novel von Willebrand factor/fibrinogen/selectin-independent, platelet adhesion-promoting function of vascular PG-M/versicans that may be relevant in normal venous thrombosis and critical in atherosclerotic conditions. A purification scheme was devised to obtain vascular versicans, which by biochemical, immunochemical, and ultrastructural means were asserted to be 1) composed primarily of isoforms V1 and V2; 2) free of contaminants; 3) prevalently substituted with chondroitin-4-sulfate and dermatan sulfate (DS) chains; and 4) capable of binding hyaluronan to form link protein-stabilized ternary complexes. Real-time analysis of human platelet perfused under diverse shear forces showed that they largely failed to bind to several vascular and nonvascular proteoglycans (PGs). In contrast, they bound in a dose- and shear rate-dependent manner to vascular versicans, exhibiting a unique attachment-detachment kinetics and establishing a firm substrate tethering characterized with no significant aggregation. Digestion of these PGs with lyases and competition experiments with purified glycosaminoglycans revealed that platelet adhesion to vascular versicans was primarily mediated by their DS chains. Incorporation of the versicans into fibrillar collagen substrates augmented their adhesive activity and strongly promoted platelet aggregation at low and high shear rates. Affinity chromatography of platelet surfaces on DS columns identified a 120-140 kDa polypeptide complex that behaved as a specific vascular versican binding membrane ligand in solid-phase binding assays. These findings indicate that selective versican variants of the subendothelium may serve as ancillary GPIbalpha/integrin/selectin-independent platelet ligands in healthy and diseased vascular beds and may be directly responsible for the platelet accruing after rupture of atherosclerotic plaques., versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation.},
  author       = {Mazzucato, M and Cozzi, M R and Pradella, P and Perissinotto, D and Malmström, Anders and Mörgelin, Matthias and Spessotto, P and Colombatti, A and De Marco, L and Perris, R},
  issn         = {1530-6860},
  keyword      = {hemostasis,shear stress,proteoglycan},
  language     = {eng},
  number       = {14},
  pages        = {1903--1916},
  publisher    = {The Federation of American Societies for Experimental Biology},
  series       = {FASEB Journal},
  title        = {Vascular PG-M/versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation},
  volume       = {16},
  year         = {2002},
}