Control of angiogenesis by galectins involves the release of platelet-derived proangiogenic factors.
Platelets contribute to vessel formation through the release of angiogenesis-modulating factors stored in their α-granules. Galectins, a family of lectins that bind β-galactoside residues, are up-regulated in inflammatory and cancerous tissues, trigger platelet activation and mediate vascularization processes. Here we aimed to elucidate whether the release of platelet-derived proangiogenic molecules could represent an alternative mechanism through which galectins promote neovascularization. We show that different members of the galectin family can selectively regulate the release of angiogenic molecules by human platelets. Whereas Galectin (Gal)-1, -3, and -8 triggered vascular endothelial growth factor (VEGF) release, only Gal-8 induced endostatin secretion. Release of VEGF induced by Gal-8 was partially prevented by COX-1, PKC, p38 and Src kinases inhibitors, whereas Gal-1-induced VEGF secretion was inhibited by PKC and ERK blockade, and Gal-3 triggered VEGF release selectively through a PKC-dependent pathway. Regarding endostatin, Gal-8 failed to stimulate its release in the presence of PKC, Src and ERK inhibitors, whereas aspirin or p38 inhibitor had no effect on endostatin release. Despite VEGF or endostatin secretion, platelet releasates generated by stimulation with each galectin stimulated angiogenic responses in vitro including endothelial cell proliferation and tubulogenesis. The platelet angiogenic activity was independent of VEGF and was attributed to the concerted action of other proangiogenic molecules distinctly released by each galectin. Thus, secretion of platelet-derived angiogenic molecules may represent an alternative mechanism by which galectins promote angiogenic responses and its selective blockade may lead to the development of therapeutic strategies for angiogenesis-related diseases.
Laboratory of Experimental Thrombosis, Institute of Experimental Medicine, CONICET-National Academy of Medicine, Buenos Aires, Argentina.
Julia
J
Etulain
Laboratory of Experimental Thrombosis, Institute of Experimental Medicine, CONICET-National Academy of Medicine, Buenos Aires, Argentina.
Soledad
S
Negrotto
Institute of Biotechnological Investigations, Technologic Institute of Chascomús-National University of San Martín, CONICET, Buenos Aires, Argentina.
María Virginia
MV
Tribulatti
Laboratory of Immunopathology, Institute of Biology and Experimental Medicine (IBYME), CONICET, Buenos Aires, Argentina.
Diego Omar
DO
Croci
Institute of Biotechnological Investigations, Technologic Institute of Chascomús-National University of San Martín, CONICET, Buenos Aires, Argentina.
Julieta
J
Carabelli
Institute of Biotechnological Investigations, Technologic Institute of Chascomús-National University of San Martín, CONICET, Buenos Aires, Argentina.
Oscar
O
Campetella
Laboratory of Immunopathology, Institute of Biology and Experimental Medicine (IBYME), CONICET, Buenos Aires, Argentina; Laboratory of Functional Glycomics, Faculty of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina.
Gabriel Adrián
GA
Rabinovich
Laboratory of Experimental Thrombosis, Institute of Experimental Medicine, CONICET-National Academy of Medicine, Buenos Aires, Argentina.
Mirta
M
Schattner
D001792:Blood Platelets / Q000378:metabolism*; D002460:Cell Line; D043169:Endostatins / Q000378:metabolism; D037483:Galectin 1 / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D018919:Neovascularization, Physiologic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043169:Endostatins; D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; C445499:LGALS1 protein, human; C091991:LGALS8 protein, human; D042461:Vascular Endothelial Growth Factor A