ROS-mediated platelet generation: a microenvironment-dependent manner for megakaryocyte proliferation, differentiation, and maturation

S Chen, Y Su, J Wang, S Chen, Y Su, J Wang

Abstract

Platelets have an important role in the body because of their manifold functions in haemostasis, thrombosis, and inflammation. Platelets are produced by megakaryocytes (MKs) that are differentiated from haematopoietic stem cells via several consecutive stages, including MK lineage commitment, MK progenitor proliferation, MK differentiation and maturation, cell apoptosis, and platelet release. During differentiation, the cells migrate from the osteoblastic niche to the vascular niche in the bone marrow, which is accompanied by reactive oxygen species (ROS)-dependent oxidation state changes in the microenvironment, suggesting that ROS can distinctly influence platelet generation and function in a microenvironment-dependent manner. The objective of this review is to reveal the role of ROS in regulating MK proliferation, differentiation, maturation, and platelet activation, thereby providing new insight into the mechanism of platelet generation, which may lead to the development of new therapeutic agents for thrombocytopenia and/or thrombosis.

Figures

Figure 1
Figure 1
Overview of all biological phases of platelet generation from HSCs and subsequent platelet activation. The abbreviated cell types are: CMP, common myeloid progenitor; BFU-E/MK, burst-forming unit erythrocyte/megakaryocyte; BFU-MK, burst-forming unit megakaryocyte; CFU-MK, colony-forming unit megakaryocyte
Figure 2
Figure 2
The distribution of MKs in their niche. MK commitment from HSCs and differentiation into immature MKs occur in the osteoblastic niche. Proplatelets then adhere to the vasculature and ultimately release individual platelets from their tips after mature MKs migrate to the vascular niche. The abbreviated cell types are: CMP, common myeloid progenitor; BFU-MK, burst-forming unit megakaryocyte
Figure 3
Figure 3
Nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent ROS production is required for all phases of megakaryocytopoiesis. ROS production or augmentation is stimulated by extracellular signals, such as cytokines, endogenous ROS, and other ligands. ROS is necessary for the complete activation of signalling pathways as a second messenger in the regulation of signal transduction during MK development, and ROS might be the central player during megakaryocytopoiesis
Figure 4
Figure 4
Proposed ROS signalling cascades and cellular biological outcomes after ROS interact with NO to generate ONOO−

References

    1. Bluteau D, Lordier L, Di Stefano A, Chang Y. Regulation of megakaryocyte maturation and platelet formation. J Thromb Haemost. 2009;7:227–234.
    1. Thon JN, Italiano JE. Platelet formation. Semin Hematol. 2010;47:220–226.
    1. Jenne CN, Urrutia R, Kubes P. Platelets: bridging hemostasis, inflammation, and immunity. Int J Lab Hematol. 2013;35:254–261.
    1. Tantry US, Bliden KP, Suarez TA, Kreutz RP, Dichiara J, Gurbel PA. Hypercoagulability, platelet function, inflammation and coronary artery disease acuity: results of the Thrombotic RIsk Progression (TRIP) study. Platelets. 2010;21:360–367.
    1. Feng W, Madajka M, Kerr BA, Mahabeleshwar GH, Whiteheart SW, Byzova TV. A novel role for platelet secretion in angiogenesis: mediating bone marrow-derived cell mobilization and homing. Blood. 2011;117:3893–3902.
    1. Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11:123–134.
    1. Reems JA, Pineault N, Sun S. In vitro megakaryocyte production and platelet biogenesis: state of the art. Transfus Med Rev. 2010;24:33–43.
    1. Botton SD, Sabri S, Daugas E, Zermati Y, Guidotti JE, Kroemer G, et al. Platelet formation is the consequence of caspase activation within megakaryocytes. Blood. 2002;100:1310–1317.
    1. Sasaki H, Hirabayashi Y, Ishibashi T, Inoue T, Matsuda M, Kai S, et al. Effects of erythropoietin, IL-3, IL-6 and LIF on a murine megakaryoblastic cell line: growth enhancement and expression of receptor mRNAs. Leuk Res. 1995;19:95–102.
    1. Burstein SA, Mei RL, Henthorn J, Friese P, Turner K. Leukemia inhibitory factor and interleukin-11 promote maturation of murine and human megakaryocytes in vitro. J Cell Physiol. 1992;153:305–312.
    1. Neben TY, Loebelenz J, Hayes L, McCarthy K, Stoudemire J, Schaub R, et al. Recombinant human interleukin-11 stimulates megakaryocytopoiesis and increases peripheral platelets in normal and splenectomized mice. Blood. 1993;81:901–908.
    1. Pang L, Weiss MJ, Poncz M. Megakaryocyte biology and related disorders. J Clin Invest. 2005;115:3332–3338.
    1. Majka M, Janowska-Wieczorek A, Ratajczak J, Kowalska MA, Vilaire G, Pan ZK, et al. Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis. Blood. 2000;96:4142–4151.
    1. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.
    1. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245–313.
    1. Reiter RJ, Tan DX, Mayo JC, Sainz RM, Leon J, Czarnocki Z. Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol. 2003;50:1129–1146.
    1. Giorgio M, Trinei M, Migliaccio E, Pelicci PG. Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals. Nat Rev Mol Cell Biol. 2007;8:722–728.
    1. Paravicini TM, Touyz RM. NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities. Diabetes Care. 2008;31:170–180.
    1. Lacy F, Gough DA, Schmid-Schonbein GW. Role of xanthine oxidase in hydrogen peroxide production. Free Radic Biol Med. 1998;25:720–727.
    1. Andrew PJ, Mayer B. Enzymatic function of nitric oxide synthases. Cardiovasc Res. 1999;43:521–531.
    1. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978;4:7–25.
    1. Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;441:1075–1079.
    1. Bianco P. Bone and the hematopoietic niche: a tale of two stem cells. Blood. 2011;117:5281–5288.
    1. Mohyeldin A, Garzon-Muvdi T, Quinones-Hinojosa A. Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell. 2010;7:150–161.
    1. Katayama Y, Battista M, Kao WM, Hidalgo A, Peired AJ, Thomas SA, et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell. 2006;124:407–421.
    1. Nagasawa T, Omatsu Y, Sugiyama T. Control of hematopoietic stem cells by the bone marrow stromal niche: the role of reticular cells. Trends Immunol. 2011;32:315–320.
    1. Kiel MJ, Morrison SJ. Uncertainty in the niches that maintain haematopoietic stem cells. Nature. 2008;8:290–301.
    1. Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell. 2004;116:769–778.
    1. Li L, Xie T. Stem cell niche: structure and function. Annu Rev Cell Dev Biol. 2005;21:605–631.
    1. Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004;118:149–161.
    1. Visnjic D, Kalajzic Z, Rowe DW, Katavic V, Lorenzo J, Aguila HL. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004;103:3258–3264.
    1. Kopp HG, Avecilla ST, Hooper AT, Rafii S. The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology. 2005;20:349–356.
    1. Li W, Johnson SA, Shelley WC, Yoder MC. Hematopoietic stem cell repopulating ability can be maintained in vitro by some primary endothelial cells. Exp Hematol. 2004;32:1226–1237.
    1. Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. 2004;10:64–71.
    1. Chow DC, Wenning LA, Miller WM, Papoutsakis ET. Modeling pO(2) distributions in the bone marrow hematopoietic compartment. II. Modified Kroghian models. Biophys J. 2001;81:685–696.
    1. Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci USA. 2007;104:5431–5436.
    1. Hermitte F, Brunet de la Grange P, Belloc F, Praloran V, Ivanovic Z. Very low O2 concentration (0.1%) favors G0 return of dividing CD34+ cells. Stem Cells. 2006;24:65–73.
    1. Ivanovic Z, Dello Sbarba P, Trimoreau F, Faucher JL, Praloran V. Primitive human HPCs are better maintained and expanded in vitro at 1 percent oxygen than at 20 percent. Transfusion. 2000;40:1482–1488.
    1. Tauro S, Hepburn MD, Bowen DT, Pippard MJ. Assessment of stromal function, and its potential contribution to deregulation of hematopoiesis in the myelodysplastic syndromes. Haematologica. 2001;86:1038–1045.
    1. Wang W, Gou L, Xie G, Tong A, He F, Lu Z, et al. Proteomic analysis of interstitial fluid in bone marrow identified that peroxiredoxin 2 regulates H(2)O(2) level of bone marrow during aging. J Proteome Res. 2010;9:3812–3819.
    1. Unwin RD, Smith DL, Blinco D, Wilson CL, Miller CJ, Evans CA, et al. Quantitative proteomics reveals posttranslational control as a regulatory factor in primary hematopoietic stem cells. Blood. 2006;107:4687–4694.
    1. Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, et al. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell. 2010;7:391–402.
    1. Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10:858–864.
    1. Danet GH, Pan Y, Luongo JL, Bonnet DA, Simon MC. Expansion of human SCID-repopulating cells under hypoxic conditions. J Clin Invest. 2003;112:126–135.
    1. Roy S, Tripathy M, Mathur N, Jain A, Mukhopadhyay A. Hypoxia improves expansion potential of human cord blood-derived hematopoietic stem cells and marrow repopulation efficiency. Eur J Haematol. 2012;88:396–405.
    1. Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1997;420:25–27.
    1. Abbas HA, Maccio DR, Coskun S, Jackson JG, Hazen AL, Sills TM, et al. Mdm2 is required for survival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity. Cell Stem Cell. 2010;7:606–617.
    1. Nakata S, Matsumura I, Tanaka H, Ezoe S, Satoh Y, Ishikawa J, et al. NF-kB family proteins participate in multiple steps of hematopoiesis through elimination of reactive oxygen species. J Biol Chem. 2004;279:55578–55586.
    1. Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell. 2007;128:325–339.
    1. Yalcin S, Marinkovic D, Mungamuri SK, Zhang X, Tong W, Sellers R, et al. ROS-mediated amplification of AKT/mTOR signalling pathway leads to myeloproliferative syndrome in Foxo3(-/-) mice. EMBO J. 2010;29:4118–4131.
    1. Rizo A, Olthof S, Han L, Vellenga E, de Haan G, Schuringa JJ. Repression of BMI1 in normal and leukemic human CD34+ cells impairs self-renewal and induces apoptosis. Blood. 2009;114:1498–1505.
    1. Miyamoto K, Araki KY, Naka K, Arai F, Takubo K, Yamazaki S, et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell. 2007;1:101–112.
    1. Jing Z, Ping Z, Yi L, Yin X, Jie W, Lingbo L. The cross-talk between ROS and p38MAPKα in the ex vivo expanded human umbilical cord blood CD133+ cells. J Huazhong Univ Sci Technol. 2011;31:591–595.
    1. Urao N, Inomata H, Razvi M, Kim HW, Wary K, McKinney R, et al. Role of nox2-based NADPH oxidase in bone marrow and progenitor cell function involved in neovascularization induced by hindlimb ischemia. Circ Res. 2008;103:212–220.
    1. Tesio M, Golan K, Corso S, Giordano S, Schajnovitz A, Vagima Y, et al. Enhanced c-Met activity promotes G-CSF-induced mobilization of hematopoietic progenitor cells via ROS signaling. Blood. 2011;117:419–428.
    1. Grek CL, Townsend DM, Tew KD. The impact of redox and thiol status on the bone marrow: pharmacological intervention strategies. Pharmacol Ther. 2011;129:172–184.
    1. Piccoli C, Ria R, Scrima R, Cela O, D'Aprile A, Boffoli D, et al. Characterization of mitochondrial and extra-mitochondrial oxygen consuming reactions in human hematopoietic stem cells. Novel evidence of the occurrence of NAD(P)H oxidase activity. J Biol Chem. 2005;280:26467–26476.
    1. Sardina JL, Lopez-Ruano G, Sanchez-Abarca LI, Perez-Simon JA, Gaztelumendi A, Trigueros C, et al. p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation. Cell Death Differ. 2010;17:1842–1854.
    1. Mostafa SS, Miller WM, Papoutsakis ET. Oxygen tension influences the differentiation, maturation and apoptosis of human megakaryocytes. Br J Haematol. 2000;111:879–889.
    1. McCrann DJ, Eliades A, Makitalo M, Matsuno K, Ravid K. Differential expression of NADPH oxidases in megakaryocytes and their role in polyploidy. Blood. 2009;114:1243–1249.
    1. Sattler M, Winkler T, Verma S, Byrne CH, Shrikhande G, Salgia R, et al. Hematopoietic growth factors signal through the formation of reactive oxygen species. Blood. 1999;93:2928–2935.
    1. Naughton R, Quiney C, Turner SD, Cotter TG. Bcr-Abl-mediated redox regulation of the PI3K/AKT pathway. Leukemia. 2009;23:1432–1440.
    1. Mazharian A, Watson SP, Severin S. Critical role for ERK1/2 in bone marrow and fetal liver-derived primary megakaryocyte differentiation, motility, and proplatelet formation. Exp Hematol. 2009;37:1238–1249.
    1. Ruiz-Gines JA, Lopez-Ongil S, Gonzalez-Rubio M, Gonzalez-Santiago L, Rodriguez-Puyol M, Rodriguez-Puyol D. Reactive oxygen species induce proliferation of bovine aortic endothelial cells. J Cardiovasc Pharmacol. 2000;35:109–113.
    1. Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol. 2004;4:181–189.
    1. del Bello B, Paolicchi A, Comporti M, Pompella A, Maellaro E. Hydrogen peroxide produced during gamma-glutamyl transpeptidase activity is involved in prevention of apoptosis and maintainance of proliferation in U937 cells. FASEB J. 1999;13:69–79.
    1. Griendling KK, Ushio-Fukai M. Redox control of vascular smooth muscle proliferation. J Lab Clin Med. 1998;132:9–15.
    1. Wartenberg M, Diedershagen H, Hescheler J, Sauer H. Growth stimulation versus induction of cell quiescence by hydrogen peroxide in prostate tumor spheroids is encoded by the duration of the Ca(2+) response. J Biol Chem. 1999;274:27759–27767.
    1. Havens CG, Ho A, Yoshioka N, Dowdy SF. Regulation of late G1/S phase transition and APC Cdh1 by reactive oxygen species. Mol Cell Biol. 2006;26:4701–4711.
    1. Pallotta I, Lovett M, Rice W, Kaplan DL, Balduini A. Bone marrow osteoblastic niche: a new model to study physiological regulation of megakaryopoiesis. PLoS One. 2009;4:e8359.
    1. Kaushansky K. The enigmatic megakaryocyte gradually reveals its secrets. Bioessays. 1999;21:353–360.
    1. Szalai G, LaRue AC, Watson DK. Molecular mechanisms of megakaryopoiesis. Cell Mol Life Sci. 2006;63:2460–2476.
    1. Xanthoudakis S, Miao G, Wang F, Pan YC, Curran T. Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J. 1992;11:3323–3335.
    1. Prata C, Maraldi T, Zambonin L, Fiorentini D, Hakim G, Landi L. ROS production and Glut1 activity in two human megakaryocytic cell lines. Biofactors. 2004;20:223–233.
    1. Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177–185.
    1. Yoshida K, Kirito K, Yongzhen H, Ozawa K, Kaushansky K, Komatsu N. Thrombopoietin (TPO) regulates HIF-1alpha levels through generation of mitochondrial reactive oxygen species. Int J Hematol. 2008;88:43–51.
    1. LaIuppa JA, Papoutsakis ET, Miller WM. Oxygen tension alters the effects of cytokines on the megakaryocyte, erythrocyte, and granulocyte lineages. Exp Hematol. 1998;26:835–843.
    1. McCrann DJ, Yang D, Chen H, Carroll S, Ravid K. Upregulation of Nox4 in the aging vasculature and its association with smooth muscle cell polyploidy. Cell Cycle. 2009;8:902–908.
    1. Eliades A, Papadantonakis N, Ravid K. New roles for cyclin E in megakaryocytic polyploidization. J Biol Chem. 2010;285:18909–18917.
    1. Wang Z, Zhang Y, Lu J, Sun S, Ravid K. Mpl ligand enhances the transcription of the cyclin D3 gene: a potential role for Sp1 transcription factor. Blood. 1999;93:4208–4221.
    1. Wang Z, Sicinski P, Weinberg RA, Zhang Y, Ravid K. Characterization of the mouse cyclin D3 gene: exon/intron organization and promoter activity. Genomics. 1996;35:156–163.
    1. Garcia P, Frampton J, Ballester A, Cales C. Ectopic expression of cyclin E allows non-endomitotic megakaryoblastic K562 cells to establish re-replication cycles. Oncogene. 2000;19:1820–1833.
    1. Junt T, Schulze H, Chen Z, Massberg S, Goerge T, Krueger A, et al. Dynamic visualization of thrombopoiesis within bone marrow. Science. 2007;317:1767–1770.
    1. O'Brien JJ, Spinelli SL, Tober J, Blumberg N, Francis CW, Taubman MB, et al. 15-Deoxy-Δ12,14-PGJ2 enhances platelet production from megakaryocytes. Blood. 2008;112:4051–4060.
    1. Mostafa SS, Papoutsakis ET, Miller WM. Oxygen tension modulates the expression of cytokine receptors, transcription factors, and lineage-specific markers in cultured human megakaryocytes. Exp Hematol. 2001;29:873–883.
    1. Mehaffey MG, Newton AL, Gandhi MJ, Crossley M, Drachman JG. X-linked thrombocytopenia caused by a novel mutation of GATA-1. Blood. 2001;98:2681–2688.
    1. Lecine P, Villeval JL, Vyas P, Swencki B, Xu Y, Shivdasani RA. Mice lacking transcription factor NF-E2 provide in vivo validation of the proplatelet model of thrombocytopoiesis and show a platelet production defect that is intrinsic to megakaryocytes. Blood. 1998;92:1608–1616.
    1. Battinelli E, Loscalzo J. Nitric oxide induces apoptosis in megakaryocytic cell lines. Blood. 2000;95:3451–3459.
    1. Battinelli E, Willoughby SR, Foxall T, Valeri CR, Loscalzo J. Induction of platelet formation from megakaryocytoid cells by nitric oxide. Proc Natl Acad Sci USA. 2001;98:14458–14463.
    1. Freedman JE, Loscalzo J, Barnard MR, Alpert C, Keaney JF, Michelson AD. Nitric oxide released from activated platelets inhibits platelet recruitment. J Clin Invest. 1997;100:350–356.
    1. Zhang P, Wang YZ, Kagan E, Bonner JC. Peroxynitrite targets the epidermal growth factor receptor, Raf-1, and MEK independently to activate MAPK. J Biol Chem. 2000;275:22479–22486.
    1. Motohashi H, Katsuoka F, Engel JD, Yamamoto M. Small Maf proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway. Proc Natl Acad Sci USA. 2004;101:6379–6384.
    1. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997;236:313–322.
    1. Katsuoka F, Motohashi H, Ishii T, Aburatani H, Engel JD, Yamamoto M. Genetic evidence that small maf proteins are essential for the activation of antioxidant response element-dependent genes. Mol Cell Biol. 2005;25:8044–8051.
    1. Chen Z, Hu M, Shivdasani RA. Expression analysis of primary mouse megakaryocyte differentiation and its application in identifying stage-specific molecular markers and a novel transcriptional target of NF-E2. Blood. 2007;109:1451–1459.
    1. Igarashi K, Kataoka K, Itoh K, Hayashi N, Nishizawa M, Yamamoto M. Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature. 1994;367:568–572.
    1. Motohashi H, Katsuoka F, Shavit JA, Engel JD, Yamamoto M. Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins. Cell. 2000;103:865–875.
    1. Motohashi H, Kimura M, Fujita R, Inoue A, Pan X, Takayama M, et al. NF-E2 domination over Nrf2 promotes ROS accumulation and megakaryocytic maturation. Blood. 2010;115:677–686.
    1. Blair P, Rex S, Vitseva O, Beaulieu L, Tanriverdi K, Chakrabarti S, et al. Stimulation of Toll-like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3-kinase. Circ Res. 2009;104:346–354.
    1. Beaulieu LM, Lin E, Morin KM, Tanriverdi K, Freedman JE. Regulatory effects of TLR2 on megakaryocytic cell function. Blood. 2011;117:5963–5974.
    1. Ray DM, Akbiyik F, Phipps RP. The peroxisome proliferator-activated receptor gamma (PPARgamma) ligands 15-deoxy-Delta12,14-prostaglandin J2 and ciglitazone induce human B lymphocyte and B cell lymphoma apoptosis by PPARgamma-independent mechanisms. J Immunol. 2006;177:5068–5076.
    1. Siddiqui NF, Shabrani NC, Kale VP, Limaye LS. Enhanced generation of megakaryocytes from umbilical cord blood-derived CD34(+) cells expanded in the presence of two nutraceuticals, docosahexanoic acid and arachidonic acid, as supplements to the cytokine-containing medium. Cytotherapy. 2011;13:114–128.
    1. Wang WQ, Zhang HF, Gao GX, Bai QX, Li R, Wang XM. Adiponectin inhibits hyperlipidemia-induced platelet aggregation via attenuating oxidative/nitrative stress. Physiol Res. 2011;60:347–354.
    1. Iuliano L, Pratico D, Ghiselli A, Bonavita MS, Violi F. Superoxide dismutase triggers activation of ‘primed' platelets. Arch Biochem Biophys. 1991;289:180–183.
    1. Handin RI, Karabin R, Boxer GJ. Enhancement of platelet function by superoxide anion. J Clin Invest. 1977;59:959–965.
    1. Ambrosio G, Golino P, Pascucci I, Rosolowsky M, Campbell WB, DeClerck F, et al. Modulation of platelet function by reactive oxygen metabolites. Am J Physiol. 1994;267:H308–H318.
    1. Del Principe D, Menichelli A, De Matteis W, Di Corpo ML, Di Giulio S, Finazzi-Agro A. Hydrogen peroxide has a role in the aggregation of human platelets. FEBS Lett. 1985;185:142–146.
    1. Pignatelli P, Pulcinelli FM, Lenti L, Gazzaniga PP, Violi F, Pignatelli BP. Hydrogen peroxide is involved in collagen-induced platelet activation. Blood. 1998;91:484–490.
    1. Seno T, Inoue N, Gao D, Okuda M, Sumi Y, Matsui K, et al. Involvement of NADH/NADPH oxidase in human platelet ROS production. Thromb Res. 2001;103:399–409.
    1. Savini I, Arnone R, Rossi A, Catani MV, Del Principe D, Avigliano L. Redox modulation of Ecto-NOX1 in human platelets. Mol Membr Biol. 2010;27:160–169.
    1. Schafer A, Wiesmann F, Neubauer S, Eigenthaler M, Bauersachs J, Channon KM. Rapid regulation of platelet activation in vivo by nitric oxide. Circulation. 2004;109:1819–1822.
    1. Clutton P, Miermont A, Freedman JE. Regulation of endogenous reactive oxygen species in platelets can reverse aggregation. Arterioscler Thromb Vasc Biol. 2004;24:187–192.
    1. Ferroni P, Vazzana N, Riondino S, Cuccurullo C, Guadagni F, Davi G. Platelet function in health and disease: from molecular mechanisms, redox considerations to novel therapeutic opportunities. Antioxid Redox Signal. 2012;17:1447–1485.
    1. Schildknecht S, van der Loo B, Weber K, Tiefenthaler K, Daiber A, Bachschmid MM. Endogenous peroxynitrite modulates PGHS-1-dependent thromboxane A2 formation and aggregation in human platelets. Free Radic Biol Med. 2008;45:512–520.
    1. Krotz F, Sohn HY, Gloe T, Zahler S, Riexinger T, Schiele TM, et al. NAD(P)H oxidase-dependent platelet superoxide anion release increases platelet recruitment. Blood. 2002;100:917–924.
    1. Begonja AJ. NO/cGMP and ROS pathways in regulation of platelet function and megakaryocyte maturation. Disertation, Julius-Maximilians University: Wurzburg; 2007.
    1. Krotz F, Sohn HY, Pohl U. Reactive oxygen species: players in the platelet game. Arterioscler Thromb Vasc Biol. 2004;24:1988–1996.
    1. O'Brien JJ, Baglole CJ, Garcia-Bates TM, Blumberg N, Francis CW, Phipps RP. 15-Deoxy-Delta12,14 prostaglandin J2-induced heme oxygenase-1 in megakaryocytes regulates thrombopoiesis. J Thromb Haemost. 2009;7:182–189.
    1. Wang J, Li L, Cang H, Shi G, Yi J. NADPH oxidase-derived reactive oxygen species are responsible for the high susceptibility to arsenic cytotoxicity in acute promyelocytic leukemia cells. Leuk Res. 2008;32:429–436.
    1. Lu J, Chew EH, Holmgren A. Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc Natl Acad Sci USA. 2007;104:12288–12293.
    1. Peeters K, Stassen JM, Collen D, Van Geet C, Freson K. Emerging treatments for thrombocytopenia: increasing platelet production. Drug Discov Today. 2008;13:798–806.
    1. Rivera J, Lozano ML, Navarro-Nunez L, Vicente V. Platelet receptors and signaling in the dynamics of thrombus formation. Haematologica. 2009;94:700–711.
    1. Pleines I, Hagedorn I, Gupta S, May F, Chakarova L, van Hengel J, et al. Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis. Blood. 2012;119:1054–1063.
    1. Antoniades C, Bakogiannis C, Tousoulis D, Demosthenous M, Marinou K, Stefanadis C. Platelet activation in atherogenesis associated with low-grade inflammation. Inflamm Allergy Drug Targets. 2010;9:334–345.
    1. Monteiro PF, Morganti RP, Delbin MA, Calixto MC, Lopes-Pires ME, Marcondes S, et al. Platelet hyperaggregability in high-fat fed rats: a role for intraplatelet reactive-oxygen species production. Cardiovasc Diabetol. 2012;11:1–9.
    1. Lakshmi SV, Padmaja G, Kuppusamy P, Kutala VK. Oxidative stress in cardiovascular disease. Indian J Biochem Biophys. 2009;46:421–440.
    1. Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens. 2000;18:655–673.
    1. Zhang N, Andresen BT, Zhang C. Inflammation and reactive oxygen species in cardiovascular disease. World J Cardiol. 2010;2:408–410.
    1. Bae JS. Antithrombotic and profibrinolytic activities of phloroglucinol. Food Chem Toxicol. 2011;49:1572–1577.
    1. Li Y, Qian ZJ, Ryu B, Lee SH, Kim MM, Kim SK. Chemical components and its antioxidant properties in vitro: an edible marine brown alga, Ecklonia cava. Bioorg Med Chem. 2009;17:1963–1973.
    1. Chang MC, Chang HH, Chan CP, Chou HY, Chang BE, Yeung SY, et al. Antiplatelet effect of phloroglucinol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A2 production. Toxicol Appl Pharmacol. 2012;263:287–295.
    1. Fassett RG, Coombes JS. Astaxanthin: a potential therapeutic agent in cardiovascular disease. Mar Drugs. 2011;9:447–465.
    1. Cai H. Hydrogen peroxide regulation of endothelial function: origins, mechanisms, and consequences. Cardiovasc Res. 2005;68:26–36.
    1. Stolk J, Hiltermann TJ, Dijkman JH, Verhoeven AJ. Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol. Am J Respir Cell Mol Biol. 1994;11:95–102.
    1. Cai H, Griendling KK, Harrison DG. The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases. Trends Pharmacol Sci. 2003;24:471–478.
    1. Diatchuk V, Lotan O, Koshkin V, Wikstroem P, Pick E. Inhibition of NADPH oxidase activation by 4-(2-aminoethyl)-benzenesulfonyl fluoride and related compounds. J Biol Chem. 1997;272:13292–13301.
    1. Drummond GR, Selemidis S, Griendling KK, Sobey CG. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov. 2011;10:453–471.

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