title: Nanoparticle-induced platelet aggregation and vascular thrombosis.
abstract: Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet-nanoparticle interactions. We studied the effects of engineered and combustion-derived carbon nanoparticles on human platelet aggregation in vitro and rat vascular thrombosis in vivo. Multiplewall (MWNT), singlewall (SWNT) nanotubes, C60 fullerenes (C60CS) and mixed carbon nanoparticles (MCN) (0.2-300 microg ml(-1)) were investigated. Nanoparticles were compared with standard urban particulate matter (SRM1648, average size 1.4 microm). Platelet function was studied using lumi aggregometry, phase-contrast, immunofluorescence and transmission electron microscopy, flow cytometry, zymography and pharmacological inhibitors of platelet aggregation. Vascular thrombosis was induced by ferric chloride and the rate of thrombosis was measured, in the presence of carbon particles, with an ultrasonic flow probe. Carbon particles, except C60CS, stimulated platelet aggregation (MCN>or=SWNT>MWNT>SRM1648) and accelerated the rate of vascular thrombosis in rat carotid arteries with a similar rank order of efficacy. All particles resulted in upregulation of GPIIb/IIIa in platelets. In contrast, particles differentially affected the release of platelet granules, as well as the activity of thromboxane-, ADP, matrix metalloproteinase- and protein kinase C-dependent pathways of aggregation. Furthermore, particle-induced aggregation was inhibited by prostacyclin and S-nitroso-glutathione, but not by aspirin. Thus, some carbon nanoparticles and microparticles have the ability to activate platelets and enhance vascular thrombosis. These observations are of importance for the pharmacological use of carbon nanoparticles and pathology of urban particulate matter.
authors.affiliation: Centre for Vascular Biology, Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Centre at Houston, 6770 Bertner Ave, Houston, TX 77025, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Radomski
authors.forename: Paul
authors.initials: P
authors.lastname: Jurasz
authors.forename: David
authors.initials: D
authors.lastname: Alonso-Escolano
authors.forename: Magdalena
authors.initials: M
authors.lastname: Drews
authors.forename: Maria
authors.initials: M
authors.lastname: Morandi
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Malinski
authors.forename: Marek W
authors.initials: MW
authors.lastname: Radomski
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002341:Carotid Artery Thrombosis / Q000139:chemically induced / Q000503:physiopathology*; D002712:Chlorides; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D005290:Ferric Compounds / Q000008:administration & dosage; D006801:Humans; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008858:Microscopy, Phase-Contrast / Q000379:methods; D049329:Nanostructures; D036103:Nanotechnology / Q000379:methods / Q000639:trends; D037742:Nanotubes, Carbon; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D037742:Nanotubes, Carbon; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D026422:S-Nitrosoglutathione; D011464:Epoprostenol; C024555:ferric chloride