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Microparticles bearing RGD peptide promote integrin αvβ3‐dependent platelet adhesion in isolated, pressurized cerebral artery
Author(s) -
Bagi Zsolt,
PerezBalderas Francisco,
Broskova Zuzana,
Davis Benjamin,
Anthony Daniel
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb494
Subject(s) - platelet , integrin , adhesion , chemistry , peptide , biophysics , microbiology and biotechnology , medicine , immunology , biochemistry , receptor , biology , organic chemistry
Platelet‐derived microvesicles (PMVs, <500 nm) play a role in thrombotic diseases. How PMVs promote platelet adhesion is poorly understood. To dissect mechanisms we established a method for real‐time imaging of microparticle (MP) and platelet adhesion in intact, perfused arteries. Platelets, with or without prior administration of arginine‐glycine‐aspartate (RGD)‐coated, ironoxide MPs (RGD‐MP, ~700nm, Alexa‐488‐enriched) were delivered intraluminally into isolated, pressurized rat cerebral artery. Individual binding events were observed with high‐speed fluorescence imaging under constant flow (10 μl/min). We detected firm binding of RGD‐MPs on endothelium surface (130±51/mm2), which was reduced by adhesion‐blocking integrin αv antibody. RGD‐MP binding was enhanced (290±73/mm2) by pro‐inflammatory cytokine TNF, which also increased vascular expression of integrin αv. Endothelial adhesion of platelets was 14±3 event/mm2 in naïve arteries, which significantly increased by TNF (48±10/mm2). Prior administration of RGD‐MPs induced greater adhesion of platelets in naïve arteries (78±10/mm2), whereas RGD peptide solution or scrambled RDG peptide‐coated MPs had no effect. Thus, we demonstrate the multivalent RGD‐MP ‐ compared to free ligand in form of RGD peptide ‐ as a more effective construct to promote αvβ3‐dependent adhesion of platelets in the intact cerebral artery.