The role of galectin-3 and galectin-3–binding protein in venous thrombosis

Galectin-3–binding protein (gal3bp) and its receptor/ligand, galectin-3 (gal3), are secreted proteins that initiate signaling cascades in several diseases, and recent human proteomic data suggest they may play a role in venous thrombosis (VT). We hypothesized that gal3bp and gal3 may promote VT. Usi...

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Published inBlood Vol. 125; no. 11; pp. 1813 - 1821
Main Authors DeRoo, Elise P., Wrobleski, Shirley K., Shea, Evelyn M., Al-Khalil, Ramsey K., Hawley, Angela E., Henke, Peter K., Myers, Daniel D., Wakefield, Thomas W., Diaz, Jose A.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 12.03.2015
American Society of Hematology
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Summary:Galectin-3–binding protein (gal3bp) and its receptor/ligand, galectin-3 (gal3), are secreted proteins that initiate signaling cascades in several diseases, and recent human proteomic data suggest they may play a role in venous thrombosis (VT). We hypothesized that gal3bp and gal3 may promote VT. Using a mouse stasis model of VT, we found that gal3bp and gal3 were localized on vein wall, red blood cells, platelets, and microparticles, whereas leukocytes expressed gal3 only. Gal3 was dramatically increased during early VT and gal3bp:gal3 colocalized in the leukocyte/endothelial cell interface, where leukocytes were partially attached to the vein wall. Thrombus size correlated with elevated gal3 and interleukin-6 (IL-6) vein wall levels. Recombinant gal3 promoted VT and increased vein wall IL-6 mRNA. Although recombinant gal3 restored the VT size in gal3−/− mice, it had no effect on IL6−/− mice, suggesting that gal3:gal3bp promotes VT through IL-6. Moreover, significantly fewer activated neutrophils were present in the gal3−/− vein walls. In a group of human patients, elevated circulating gal3bp correlated with acute VT. In conclusion, gal3bp:gal3 play a critical role in VT, likely via IL-6 and PMN-mediated thrombotic mechanisms, and may be a potential biomarker in human VT. •We determined the location of gal3bp and gal3 and their role in promoting VT and leukocyte/endothelial cell interactions for the first time.•Gal3bp and gal3 have the potential to be used as targets for future VT therapies.
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ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2014-04-569939