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Heterogeneous glycosylation patterns of human PAI-1 may reveal its cellular origin.

Författare och institution:
Helén Brogren (Institutionen för medicin, avdelningen för akut och kardiovaskulär medicin); Carina Sihlbom (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Karin Wallmark (Institutionen för medicin, avdelningen för akut och kardiovaskulär medicin); Malin Lönn (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Johanna Deinum (-); Lena Karlsson (Institutionen för medicin, avdelningen för akut och kardiovaskulär medicin); Sverker Jern (Institutionen för medicin, avdelningen för akut och kardiovaskulär medicin)
Publicerad i:
Thrombosis research, 122 ( 2 ) s. 271-81
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
The main inhibitor of intravascular fibrinolysis is plasminogen activator inhibitor 1 (PAI-1) which binds to and irreversibly inhibits tissue plasminogen activator (tPA). PAI-1 is present in blood, both in platelets and in plasma, and PAI-1 levels are associated with risk of atherothrombosis. Several tissues express PAI-1 but the source of plasma PAI-1 is not known. We recently found that platelets can de novo synthesize PAI-1 and the amount synthesized in vitro in 24 hours is 35-fold higher than required to maintain normal plasma levels. Recombinant human PAI-1 expressed in different cell types or secreted naturally by human cell lines, exhibit heterogeneous glycosylation patterns. The aim of this study was to investigate the hypothesis that platelets might be the source of plasma PAI-1 and that the cellular source of PAI-1 can be determined by its tissue-specific glycosylation pattern. PAI-1 was isolated from platelets, macrophages, endothelial cells, adipose tissue, as well as plasma from lean and obese subjects. The glycosylation was analyzed by nanoLC-MS/MS. PAI-1 isolated from cell lysates and conditioned media from macrophages, endothelial cells, and adipose tissue expressed heterogeneous glycosylation patterns. By contrast, no glycans were detected on PAI-1 isolated from plasma or platelets from healthy lean individuals. Hence, our data suggest that platelets may be the main source of plasma PAI-1 in lean individuals. Interestingly, plasma PAI-1 from obese subjects had a glycan composition similar to that of adipose tissue suggesting that obese subjects with elevated PAI-1 levels may have a major contribution from other tissues.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Kardiologi ->
Kardiovaskulär medicin
Adipose Tissue, metabolism, Adult, Blood Platelets, metabolism, Endothelial Cells, cytology, metabolism, Female, Fibrinolysis, Glycosylation, Hepatocytes, cytology, Humans, Macrophages, cytology, metabolism, Middle Aged, Models, Biological, Monocytes, cytology, Plasminogen Activator Inhibitor 1, chemistry, Recombinant Proteins, chemistry
Postens nummer:
Posten skapad:
2010-01-22 15:50
Posten ändrad:
2010-02-25 13:22

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