Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Platelet Shape Changes and Cytoskeleton Dynamics as Novel Therapeutic Targets for Anti-Thrombotic Drugs

  • Shin, Eun-Kyung (College of Pharmacy, Seoul National University) ;
  • Park, Hanseul (College of Pharmacy, Ewha Womans University) ;
  • Noh, Ji-Yoon (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lim, Kyung-Min (College of Pharmacy, Ewha Womans University) ;
  • Chung, Jin-Ho (College of Pharmacy, Seoul National University)
  • Received : 2016.06.27
  • Accepted : 2016.09.01
  • Published : 2017.05.01
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Abstract

Platelets play an essential role in hemostasis through aggregation and adhesion to vascular injury sites but their unnecessary activation can often lead to thrombotic diseases. Upon exposure to physical or biochemical stimuli, remarkable platelet shape changes precede aggregation or adhesion. Platelets shape changes facilitate the formation and adhesion of platelet aggregates, but are readily reversible in contrast to the irrevocable characteristics of aggregation and adhesion. In this dynamic phenomenon, complex molecular signaling pathways and a host of diverse cytoskeleton proteins are involved. Platelet shape change is easily primed by diverse pro-thrombotic xenobiotics and stimuli, and its inhibition can modulate thrombosis, which can ultimately contribute to the development or prevention of thrombotic diseases. In this review, we discussed the current knowledge on the mechanisms of platelet shape change and also pathological implications and therapeutic opportunities for regulating the related cytoskeleton dynamics.

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References

  1. Abrescia, P. and Golino, P. (2005) Free radicals and antioxidants in cardiovascular diseases. Expert Rev. Cardiovasc. Ther. 3, 159-171. https://doi.org/10.1586/14779072.3.1.159
  2. Bennett, J. S., Zigmond, S., Vilaire, G., Cunningham, M. E. and Bednar, B. (1999) The platelet cytoskeleton regulates the affinity of the integrin ${\alpha}IIb{\beta}3$ for fibrinogen. J. Biol. Chem. 274, 25301-25307. https://doi.org/10.1074/jbc.274.36.25301
  3. Berridge, M. J., Lipp, P. and Bootman, M. D. (2000) The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell Biol. 1, 11-21.
  4. Born, G. V., Dearnley, R., Foulks, J. G. and Sharp, D. E. (1978) Quantification of the morphological reaction of platelets to aggregating agents and of its reversal by aggregation inhibitors. J. Physiol. 280, 193-212. https://doi.org/10.1113/jphysiol.1978.sp012380
  5. Coller, B. S. (2013) Foreword - A brief history of ideas about platelets in health and disease. In Platelets (A. D. Michelson, Ed.), pp. xix-xliv. Academic Press.
  6. Collins, B. and Hollidge, C. (2003) Antithrombotic drug market. Nat. Rev. Drug Discov. 2, 11-12. https://doi.org/10.1038/nrd966
  7. Colman, R. W., Nachmias, V. T., Cines, D. B. and Schreiber, A. D. (1983) Effect of antiplatelet antibody on platelet shape change, volume, and morphology. Am. J. Physiol. 244, H357-H361.
  8. Crowley, S. D., Gurley, S. B., Herrera, M. J., Ruiz, P., Griffiths, R., Kumar, A. P., Kim, H.-S., Smithies, O., Le, T. H. and Coffman, T. M. (2006) Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc. Natl. Acad. Sci. U.S.A. 103, 17985-17990. https://doi.org/10.1073/pnas.0605545103
  9. Daniel, J. L., Molish, I. R., Rigmaiden, M. and Stewart, G. (1984) Evidence for a role of myosin phosphorylation in the initiation of the platelet shape change response. J. Biol. Chem. 259, 9826-9831.
  10. Dayal, S., Pati, H. P., Pande, G. K., Sharma, P. and Saraya, A. K. (1995) Platelet ultra-structure study in Budd-Chiari syndrome. Eur. J. Haematol. 55, 294-301.
  11. Escolar, G., Leistikow, E. and White, J. G. (1989) The fate of the open canalicular system in surface and suspension-activated platelets. Blood 74, 1983-1988.
  12. Estevez, B., Stojanovic-Terpo, A., Delaney, M. K., O'Brien, K. A., Berndt, M. C., Ruan, C. and Du, X. (2013) LIM kinase-1 selectively promotes glycoprotein Ib-IX-mediated TXA2 synthesis, platelet activation, and thrombosis. Blood 121, 4586-4594. https://doi.org/10.1182/blood-2012-12-470765
  13. Fox, J. E. and Phillips, D. R. (1981) Inhibition of actin polymerization in blood platelets by cytochalasins. Nature 292, 650-652. https://doi.org/10.1038/292650a0
  14. Furman, M. I., Gardner, T. M. and Goldschmidt-Clermont, P. J. (1993) Mechanisms of cytoskeletal reorganization during platelet activation. Thromb. Haemost. 70, 229-232. https://doi.org/10.1055/s-0038-1646196
  15. Haaland, H. D. and Holmsen, H. (2011) Potentiation by adrenaline of agonist-induced responses in normal human platelets in vitro. Platelets 22, 328-337. https://doi.org/10.3109/09537104.2011.551949
  16. Hartwig, J. H. (1992) Mechanisms of actin rearrangements mediating platelet activation. J. Cell Biol. 118, 1421-1442. https://doi.org/10.1083/jcb.118.6.1421
  17. Hartwig, J. H. (2013) Chapter 8 - The Platelet Cytoskeleton A2. In Platelets (A. D. Michelson, Ed.), pp. 145-168. Academic Press.
  18. Hartwig, J. H., Barkalow, K., Azim, A. and Italiano, J. (1999) The elegant platelet: signals controlling actin assembly. Thromb. Haemost. 82, 392-398. https://doi.org/10.1055/s-0037-1615858
  19. Hartwig, J. H., Bokoch, G. M., Carpenter, C. L., Janmey, P. A., Taylor, L. A., Toker, A. and Stossel, T. P. (1995) Thrombin receptor ligation and activated Rac uncap actin filament barbed ends through phosphoinositide synthesis in permeabilized human platelets. Cell 82, 643-653. https://doi.org/10.1016/0092-8674(95)90036-5
  20. Heasman, S. J. and Ridley, A. J. (2008) Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat. Rev. Mol. Cell Biol. 9, 690-701. https://doi.org/10.1038/nrm2476
  21. Jackson, S. P. (2007) The growing complexity of platelet aggregation. Blood 109, 5087-5095. https://doi.org/10.1182/blood-2006-12-027698
  22. Jagroop, I. A. and Mikhailidis, D. P. (2000) Angiotensin II can induce and potentiate shape change in human platelets: effect of losartan. J. Hum. Hypertens. 14, 581-585. https://doi.org/10.1038/sj.jhh.1001102
  23. Janowska-Wieczorek, A., Marquez-Curtis, L. A., Wysoczynski, M. and Ratajczak, M. Z. (2006) Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion 46, 1199-1209. https://doi.org/10.1111/j.1537-2995.2006.00871.x
  24. Jennrich, P. (2013) The influence of arsenic, lead, and mercury on the development of cardiovascular diseases. ISRN Hypertens. 2013, 234034.
  25. Jun, E. A., Lim, K. M., Kim, K., Bae, O. N., Noh, J. Y., Chung, K. H. and Chung, J. H. (2011) Silver nanoparticles enhance thrombus formation through increased platelet aggregation and procoagulant activity. Nanotoxicology 5, 157-167. https://doi.org/10.3109/17435390.2010.506250
  26. Jurak Begonja, A., Hoffmeister, K. M., Hartwig, J. H. and Falet, H. (2011) FlnA-null megakaryocytes prematurely release large and fragile platelets that circulate poorly. Blood 118, 2285-2295. https://doi.org/10.1182/blood-2011-04-348482
  27. Kanaji, T., Ware, J., Okamura, T. and Newman, P. J. (2012) $GPIb{\alpha}$ regulates platelet size by controlling the subcellular localization of filamin. Blood 119, 2906-2913. https://doi.org/10.1182/blood-2011-08-376566
  28. Kashiwagi, H., Shiraga, M., Kato, H., Kamae, T., Yamamoto, N., Tadokoro, S., Kurata, Y., Tomiyama, Y. and Kanakura, Y. (2005) Negative regulation of platelet function by a secreted cell repulsive protein, semaphorin 3A. Blood 106, 913-921. https://doi.org/10.1182/blood-2004-10-4092
  29. Kim, M., Han, C. H. and Lee, M. Y. (2014) NADPH oxidase and the cardiovascular toxicity associated with smoking. Toxicol. Res. 30, 149-157. https://doi.org/10.5487/TR.2014.30.3.149
  30. Klages, B., Brandt, U., Simon, M. I., Schultz, G. and Offermanns, S. (1999) Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. J. Cell Biol. 144, 745-754. https://doi.org/10.1083/jcb.144.4.745
  31. Knijff-Dutmer, E., Koerts, J., Nieuwland, R., Kalsbeek-Batenburg, E. and Van De Laar, M. (2002) Elevated levels of platelet microparticles are associated with disease activity in rheumatoid arthritis. Arthritis Rheum. 46, 1498-1503. https://doi.org/10.1002/art.10312
  32. Kovacsovics, T. J. and Hartwig, J. H. (1996) Thrombin-induced GPIb-IX centralization on the platelet surface requires actin assembly and myosin II activation. Blood 87, 618-629.
  33. Kuhn, S. and Geyer, M. (2014) Formins as effector proteins of Rho GTPases. Small GTPases 5, e29513.
  34. Kuwahara, M., Sugimoto, M., Tsuji, S., Matsui, H., Mizuno, T., Miyata, S. and Yoshioka, A. (2002) Platelet shape changes and adhesion under high shear flow. Arterioscler. Thromb. Vasc. Biol. 22, 329-334. https://doi.org/10.1161/hq0202.104122
  35. Lefebvre, P., White, J., Krumwiede, M. and Cohen, I. (1993) Role of actin in platelet function. Eur. J. Cell Biol. 62, 194-204.
  36. Liu, Y., Yin, H., Jiang, Y., Xue, M., Guo, C., Shi, D. and Chen, K. (2013) Correlation between platelet gelsolin and platelet activation level in acute myocardial infarction rats and intervention effect of effective components of chuanxiong rhizome and red peony root. Evid. Based Complement. Alternat. Med. 2013, 985746.
  37. Macfarlane, D. E. (1981) The effects of methyl mercury on platelets: induction of aggregation and release via activation of the prostaglandin synthesis pathway. Mol. Pharmacol. 19, 470-476.
  38. Matarrese, P., Straface, E., Palumbo, G., Anselmi, M., Gambardella, L., Ascione, B., Del Principe, D. and Malorni, W. (2009) Mitochondria regulate platelet metamorphosis induced by opsonized zymosan A-activation and long-term commitment to cell death. FEBS J. 276, 845-856. https://doi.org/10.1111/j.1742-4658.2008.06829.x
  39. Maurer-Spurej, E. and Devine, D. V. (2001) Platelet aggregation is not initiated by platelet shape change. Lab. Invest. 81, 1517-1525. https://doi.org/10.1038/labinvest.3780365
  40. Miki, H., Suetsugu, S. and Takenawa, T. (1998) WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. EMBO J. 17, 6932-6941. https://doi.org/10.1093/emboj/17.23.6932
  41. Milioli, M., Ibanez-Vea, M., Sidoli, S., Palmisano, G., Careri, M. and Larsen, M. R. (2015) Quantitative proteomics analysis of plateletderived microparticles reveals distinct protein signatures when stimulated by different physiological agonists. J. Proteomics 121, 56-66. https://doi.org/10.1016/j.jprot.2015.03.013
  42. Milton, J. G. and Frojmovic, M. M. (1984) Adrenaline and adenosine diphosphate-induced platelet aggregation require shape change. Importance of pseudopods. J. Lab. Clin. Med. 104, 805-815.
  43. Mountford, J. K., Petitjean, C., Putra, H. W., McCafferty, J. A., Setiabakti, N. M., Lee, H., Tonnesen, L. L., McFadyen, J. D., Schoenwaelder, S. M., Eckly, A., Gachet, C., Ellis, S., Voss, A. K., Dickins, R. A., Hamilton, J. R. and Jackson, S. P. (2015) The class II PI 3-kinase, $PI3KC2{\alpha}$, links platelet internal membrane structure to shear-dependent adhesive function. Nat. Commun. 6, 6535. https://doi.org/10.1038/ncomms7535
  44. Nakamura, F., Stossel, T. P. and Hartwig, J. H. (2011) The filamins: organizers of cell structure and function. Cell Adh. Migr. 5, 160-169. https://doi.org/10.4161/cam.5.2.14401
  45. Natarajan, P., May, J. A., Sanderson, H. M., Zabe, M., Spangenberg, P. and Heptinstall, S. (2000) Effects of cytochalasin H, a potent inhibitor of cytoskeletal reorganisation, on platelet function. Platelets 11, 467-476. https://doi.org/10.1080/09537100020027842
  46. Nesbitt, W. S., Westein, E., Tovar-Lopez, F. J., Tolouei, E., Mitchell, A., Fu, J., Carberry, J., Fouras, A. and Jackson, S. P. (2009) A shear gradient-dependent platelet aggregation mechanism drives thrombus formation. Nat. Med. 15, 665-673. https://doi.org/10.1038/nm.1955
  47. Nomura, S., Uehata, S., Saito, S., Osumi, K., Ozeki, Y. and Kimura, Y. (2003) Enzyme immunoassay detection of platelet-derived microparticles and RANTES in acute coronary syndrome. Thromb. Haemost. 89, 506-512. https://doi.org/10.1055/s-0037-1613381
  48. Nurden, A. T. (2006) Glanzmann thrombasthenia. Orphanet J. Rare Dis. 1, 10. https://doi.org/10.1186/1750-1172-1-10
  49. Offermanns, S., Toombs, C. F., Hu, Y. H. and Simon, M. I. (1997) Defective platelet activation in $G{\alpha}q$-deficient mice. Nature 389, 183-186. https://doi.org/10.1038/38284
  50. Ohlmann, P., Eckly, A., Freund, M., Cazenave, J. P., Offermanns, S. and Gachet, C. (2000) ADP induces partial platelet aggregation without shape change and potentiates collagen-induced aggregation in the absence of $G{\alpha}q$. Blood 96, 2134-2139.
  51. Paul, B. Z., Daniel, J. L. and Kunapuli, S. P. (1999) Platelet shape change is mediated by both calcium-dependent and -independent signaling pathways. Role of p160 Rho-associated coiled-coil-containing protein kinase in platelet shape change. J. Biol. Chem. 274, 28293-28300. https://doi.org/10.1074/jbc.274.40.28293
  52. Radomski, A., Jurasz, P., Alonso-Escolano, D., Drews, M., Morandi, M., Malinski, T. and Radomski, M. W. (2005) Nanoparticle-induced platelet aggregation and vascular thrombosis. Br. J. Pharmacol. 146, 882-893. https://doi.org/10.1038/sj.bjp.0706386
  53. Rao, A. K., Vaidyula, V. R., Bagga, S., Jalagadugula, G., Gaughan, J., Wilhite, D. B. and Comerota, A. J. (2006) Effect of antiplatelet agents clopidogrel, aspirin, and cilostazol on circulating tissue factor procoagulant activity in patients with peripheral arterial disease. Thromb. Haemost. 96, 738-743. https://doi.org/10.1160/TH06-08-0451
  54. Ren, Q., Barber, H. K., Crawford, G. L., Karim, Z. A., Zhao, C., Choi, W., Wang, C. C., Hong, W. and Whiteheart, S. W. (2007) Endobrevin/ VAMP-8 is the primary v-SNARE for the platelet release reaction. Mol. Biol. Cell 18, 24-33. https://doi.org/10.1091/mbc.e06-09-0785
  55. Retzer, M. and Essler, M. (2000) Lysophosphatidic acid-induced platelet shape change proceeds via Rho/Rho kinase-mediated myosin light-chain and moesin phosphorylation. Cell. Signal. 12, 645-648. https://doi.org/10.1016/S0898-6568(00)00108-X
  56. Rohatgi, R., Ma, L., Miki, H., Lopez, M., Kirchhausen, T., Takenawa, T. and Kirschner, M. W. (1999) The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 97, 221-231. https://doi.org/10.1016/S0092-8674(00)80732-1
  57. Sanderson, H. M., Heptinstall, S., Vickers, J. and Losche, W. (1996) Studies on the effects of agonists and antagonists on platelet shape change and platelet aggregation in whole blood. Blood Coagul. Fibrinolysis 7, 245-248. https://doi.org/10.1097/00001721-199603000-00034
  58. Sandmann, R. and Koster, S. (2016) Topographic cues reveal two distinct spreading mechanisms in blood platelets. Sci. Rep. 6, 22357.
  59. Savouret, J. F., Berdeaux, A. and Casper, R. (2003) The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases. Nutr. Metab. Cardiovasc. Dis. 13, 104-113. https://doi.org/10.1016/S0939-4753(03)80026-1
  60. Schraw, T. D., Lemons, P. P., Dean, W. L. and Whiteheart, S. W. (2003) A role for Sec1/Munc18 proteins in platelet exocytosis. Biochem. J. 374, 207-217. https://doi.org/10.1042/bj20030610
  61. Smyth, E., Solomon, A., Vydyanath, A., Luther, P. K., Pitchford, S., Tetley, T. D. and Emerson, M. (2015) Induction and enhancement of platelet aggregation in vitro and in vivo by model polystyrene nanoparticles. Nanotoxicology 9, 356-364. https://doi.org/10.3109/17435390.2014.933902
  62. Smyth, S. S., Whiteheart, S., Italiano, J. E. J. and Coller, B. S. (2010) Platelet morphology, biochemistry, and function. In Williams Hematology (K. Kaushansky, E. Beutler, U. Seligsohn, M. A. Lichtman, T. J. Kipps and J. T. Prchal), pp. 1735-1814. The McGraw-Hill Companies, Inc.
  63. Tadokoro, S., Shattil, S. J., Eto, K., Tai, V., Liddington, R. C., de Pereda, J. M., Ginsberg, M. H. and Calderwood, D. A. (2003) Talin binding to integrin b tails: a final common step in integrin activation. Science 302, 103-106. https://doi.org/10.1126/science.1086652
  64. Thon, J. N. and Italiano, J. E., Jr. (2012) Does size matter in platelet production? Blood 120, 1552-1561. https://doi.org/10.1182/blood-2012-04-408724
  65. Tolmachova, T., Abrink, M., Futter, C. E., Authi, K. S. and Seabra, M. C. (2007) Rab27b regulates number and secretion of platelet dense granules. Proc. Natl. Acad. Sci. U.S.A. 104, 5872-5877. https://doi.org/10.1073/pnas.0609879104
  66. Torti, M., Festetics, E. T., Bertoni, A., Sinigaglia, F. and Balduini, C. (1996) Agonist-induced actin polymerization is required for the irreversibility of platelet aggregation. Thromb. Haemost. 76, 444-449. https://doi.org/10.1055/s-0038-1650597
  67. Van Poucke, S., Stevens, K., Marcus, A. E. and Lance, M. (2014) Hypothermia: effects on platelet function and hemostasis. Thromb. J. 12, 31. https://doi.org/10.1186/s12959-014-0031-z
  68. Wannemacher, K. M., Wang, L., Zhu, L. and Brass, L. F. (2011) The role of semaphorins and their receptors in platelets: Lessons learned from neuronal and immune synapses. Platelets 22, 461-465. https://doi.org/10.3109/09537104.2011.561891
  69. White, J. G. and Clawson, C. C. (1980) The surface-connected canalicular system of blood platelets--a fenestrated membrane system. Am. J. Pathol. 101, 353-364.
  70. Winokur, R. and Hartwig, J. H. (1995) Mechanism of shape change in chilled human platelets. Blood 85, 1796-1804.
  71. Zheng, Y., Adams, T., Zhi, H., Yu, M., Wen, R., Newman, P. J., Wang, D. and Newman, D. K. (2015) Restoration of responsiveness of phospholipase $C{\gamma}2$-deficient platelets by enforced expression of phospholipase $C{\gamma}1$. PLoS ONE 10, e0119739. https://doi.org/10.1371/journal.pone.0119739
  72. Zhu, L., Bergmeier, W., Wu, J., Jiang, H., Stalker, T. J., Cieslak, M., Fan, R., Boumsell, L., Kumanogoh, A., Kikutani, H., Tamagnone, L., Wagner, D. D., Milla, M. E. and Brass, L. F. (2007) Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc. Natl. Acad. Sci. U.S.A. 104, 1621-1626. https://doi.org/10.1073/pnas.0606344104

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