title: Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli.
abstract: The present study characterized platelet secretion and surface expression of proangiogenic stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) and antiangiogenic PF4 and endostatin on activation. The angiogenic factors presented in randomly distributed granules in resting platelets, which were peripherized on activation. Confocal and immunogold electron microscopy demonstrated that SDF-1α/CXCL12 and PF4/CXCL4 mostly present in different granules. Platelet activation induced marked SDF-1α and endostatin but mild PF4 or no VEGF surface expression. PAR1-activating peptide (PAR1-AP), adenosine diphosphate (via P2Y1/P2Y12), and glycoprotein VI-targeting collagen-related peptide induced massive SDF-1α and VEGF but modest PF4 or no endostatin release. In contrast, PAR4-AP triggered marked PF4 and sole endostatin release but limited SDF-1α or VEGF secretion. Distinct platelet release of SDF-1α and endostatin involved different engagements of intracellular signaling pathways. In conclusion, different platelet stimuli evoke distinct secretion and surface expression of proangiogenic and antiangiogenic factors. PAR1, adenosine diphosphate, and glycoprotein VI stimulation favors proangiogenic, whereas PAR4 promotes antiangiogenic, factor release.
authors.affiliation: Department of Medicine, Clinical Pharmacology Unit, Karolinska Institutet at Karolinska University Hospital (Solna), Stockholm, Sweden.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Chatterjee
authors.forename: Zhangsen
authors.initials: Z
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Kjell
authors.initials: K
authors.lastname: Hultenby
authors.forename: Linjing
authors.initials: L
authors.lastname: Zhu
authors.forename: Hu
authors.initials: H
authors.lastname: Hu
authors.forename: Gunnar P
authors.initials: GP
authors.lastname: Nilsson
authors.forename: Nailin
authors.initials: N
authors.lastname: Li
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D043169:Endostatins / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000819:agonists; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; C515255:CXCL12 protein, human; D002352:Carrier Proteins; D054377:Chemokine CXCL12; D043169:Endostatins; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D044463:Receptor, PAR-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C455901:alanyl-tyrosyl-prolyl-glycyl-lysyl-phenylalanine; C435908:collagen-related peptide