title: Glycoprotein IIb/IIIa and P2Y12 induction by oligochitosan accelerates platelet aggregation.
abstract: Platelet membrane receptor glycoprotein IIb/IIIa (gpiibiiia) is a receptor detected on platelets. Adenosine diphosphate (ADP) activates gpiibiiia and P2Y12, causing platelet aggregation and thrombus stabilization during blood loss. Chitosan biomaterials were found to promote surface induced hemostasis and were capable of activating blood coagulation cascades by enhancing platelet aggregation. Our current findings show that the activation of the gpiibiiia complex and the major ADP receptor P2Y12 is required for platelet aggregation to reach hemostasis following the adherence of various concentrations of chitosan biomaterials [7% N,O-carboxymethylchitosan (NO-CMC) with 0.45 mL collagen, 8% NO-CMC, oligochitosan (O-C), and oligochitosan 53 (O-C 53)]. We studied gpiibiiia and P2Y12 through flow cytometric analysis and western blotting techniques. The highest expression of gpiibiiia was observed with Lyostypt (74.3 ± 7.82%), followed by O-C (65.5 ± 7.17%). Lyostypt and O-C resulted in gpiibiiia expression increases of 29.2% and 13.9%, respectively, compared with blood alone. Western blot analysis revealed that only O-C 53 upregulated the expression of P2Y12 (1.12 ± 0.03-fold) compared with blood alone. Our findings suggest that the regulation of gpiibiiia and P2Y12 levels could be clinically useful to activate platelets to reach hemostasis. Further, we show that the novel oligochitosan is able to induce the increased expression of gpiibiiia and P2Y12, thus accelerating platelet aggregation in vitro.
authors.affiliation: Reconstructive Sciences Unit, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors.forename: Mercy Halleluyah
authors.identifier: 0000-0001-7023-7802
authors.initials: MH
authors.lastname: Periayah
authors.affiliation: Reconstructive Sciences Unit, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors.forename: Ahmad Sukari
authors.initials: AS
authors.lastname: Halim
authors.affiliation: Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors.forename: Nik Soriani
authors.identifier: 0000-0002-9679-6917
authors.initials: NS
authors.lastname: Yaacob
authors.affiliation: Reconstructive Sciences Unit, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors.forename: Arman Zaharil Mat
authors.identifier: 0000-0002-4003-6783
authors.initials: AZ
authors.lastname: Saad
authors.affiliation: Advanced Medical & Dental Institute, Universiti Sains Malaysia, No. 1-8, Persiaran, Seksyen 4/1, Bandar Putra Bertam, 13200 Kepala Batas, Pulau Pinang, Malaysia.
authors.forename: Abdul Rahim
authors.initials: AR
authors.lastname: Hussein
authors.affiliation: Industrial Biotechnology Research Centre, SIRIM Berhad, No. 1 Persiaran Dato' Menteri, Section 2, P.O. Box 7035, 40700 Shah Alam, Selangor, Malaysia.
authors.forename: Ahmad Hazri Abdul
authors.identifier: 0000-0001-8617-7103
authors.initials: AH
authors.lastname: Rashid
authors.affiliation: Industrial Biotechnology Research Centre, SIRIM Berhad, No. 1 Persiaran Dato' Menteri, Section 2, P.O. Box 7035, 40700 Shah Alam, Selangor, Malaysia.
authors.forename: Zanariah
authors.initials: Z
authors.lastname: Ujang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048271:Chitosan; D006801:Humans; D009844:Oligosaccharides; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*
chemical_list: D009844:Oligosaccharides; C548576:P2RY12 protein, human; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D058925:Receptors, Purinergic P2Y12; C493484:oligochitosan; D002686:Chitin; D000255:Adenosine Triphosphate; D048271:Chitosan