Thromb Haemost 2011; 106(01): 75-82
DOI: 10.1160/TH10-11-0765
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Platelet factor XIII gene expression and embolic propensity in atrial fibrillation

Izabella Gosk-Bierska
1   Mayo Clinic and Foundation for Education and Research, Rochester, Minnesota, USA
2   University Medical School of Wroclaw, Poland
,
Robert D. McBane
1   Mayo Clinic and Foundation for Education and Research, Rochester, Minnesota, USA
,
Yanhong Wu
1   Mayo Clinic and Foundation for Education and Research, Rochester, Minnesota, USA
,
Jozef Mruk
3   Department of Internal Medicine, Universityof Kansas School of Medicine-Wichita, Witchita, Kansas, USA
4   Wichita Clinic, Wichita, Kansas, USA
,
Alfonso Tafur
1   Mayo Clinic and Foundation for Education and Research, Rochester, Minnesota, USA
,
Thomas McLeod
1   Mayo Clinic and Foundation for Education and Research, Rochester, Minnesota, USA
,
Waldemar E. Wysokinski
1   Mayo Clinic and Foundation for Education and Research, Rochester, Minnesota, USA
› Institutsangaben
Financial support: This work was supported by CR 92568 grant from the Department of Internal Medicine, Mayo Clinic and biostatistical support was provided by an internal grant from the Mayo Clinic Division of Cardiology.
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Publikationsverlauf

Received: 06. Dezember 2010

Accepted after major revision: 25. April 2011

Publikationsdatum:
24. November 2017 (online)

Summary

Nearly 15% of patients with non-valvular atrial fibrillation (NVAF) have left atrial appendage thrombus (LAAT) by transesophageal echocardiography (TEE) and yet the annual stroke rate averages 5%. The aim of this study was to identify variables influencing embolic propensity of LAAT. Platelet RNA was extracted from platelet-rich regions within formalin- fixed, paraffin-embedded specimens obtained from NVAF patients during cardiac surgery (26 LAAT from 23 patients) or peripheral embolectomy (51 thrombi from 41 patients). Platelet RNA was also assessed from whole blood from 40 NVAF patients. Expression of six platelet- predominate genes: H2A histone family, A1 domain of factor XIII, integrin α2bβ3; glycoprotein IX, platelet factor 4, glycoprotein Ib, was performed using TaqMan MGB-probe based quantitative real-time polymerase chain reaction. Platelet factor XIII subunit A gene expression was significantly lower in embolised compared to non-embolised thrombi as determined by normalised cycle threshold values (4.0 ± 1.2 v 2.8 ± 1.8, p=0.02). Expression of other genes did not differ by embolic status. In conclusion, RNA extracted from formalin-fixed, paraffin-embedded platelet-rich tissues can be used for analysis of platelet- predominate gene expression. Variable factor XIII gene expression in thrombi generated during NVAF may in part explain the propensity to embolisation.

 
  • References

  • 1 Aberg H. Atrial fibrillation. I.A study of atrial thrombosis and systemic embolismin a necropsy material. Acta Med Scand 1969; 185: 373-379.
  • 2 Manning WJ, Silverman DI, Waksmonski CA. et al. Prevalence of residual left at-rial thrombi among patients with acute thromboembolism and newly recognizedatrial fibrillation. Arch Intern Med 1995; 155: 2193-2198.
  • 3 Klein AL, Grimm RA, Murray RD. et al. Use of transesophageal echocardiographyto guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001; 344: 1411-1420.
  • 4 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factorfor stroke: The Framingham Study. Stroke 1991; 22: 983-988.
  • 5 Miller VT, Rothrock JF, Pearce LA. et al. Ischemic stroke in patients with atrial fi-brillation: effect of aspirin according to stroke mechanism. Stroke Prevention inAtrial Fibrillation Investigators. Neurology 1993; 43: 32-36.
  • 6 Hart RG, Pearce LA, Miller VT. et al. Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies. Cerebrovasc Dis 2000; 10: 39-43.
  • 7 Wysokinski WE, Ammash N, Sobande F. et al. CHADS2 and echocardiographic predictors of left atrial thrombus in non-valvular atrial fibrillation. Am Heart J 2010; 159: 665-671.
  • 8 Wysokinski WE, Owen WG, Fass DN. et al. Atrial Fibrillation and Thrombosis: Immunohistochemical Differences between In Situ and Embolized. J Thromb Haemost 2004; 2: 1637-1644
  • 9 Thompson CB, Eaton KA, Princiotta SM. et al. Size dependent platelet subpopulations: relationship of platelet volume to ultrastructure, enzymatic activity and function. Br J Haematol 1982; 50: 509-519.
  • 10 Giles H, Smith REA, Martin JF. Platelet glycoprotein IIb/IIIa and size are increased in acute myocardial infarction. Eur J Clin Invest 1994; 24: 69-72.
  • 11 Bath P, Algert C, Chapman N. et al. Association of mean platelet volume with risk of stroke among 3134 individuals with history of cerebrovascular disease. Stroke 2004; 35: 622-626.
  • 12 Alberio LJ, Clemetson KJ. All platelets are not equal: COAT platelets. Curr Hematol Rep 2004; 3: 338-343.
  • 13 Colkesen Y, Acil T, Abayli B. et al. Mean platelet volume is elevated during paroxysmal atrial fibrillation: a marker of increased platelet activation?. Blood Coagul Fibrinolysis 2008; 19: 411-414.
  • 14 Weyrich AS, Dixon DA, Pabla R. et al. Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets. Proc Natl Acad Sci USA 1998; 95: 5556-5561
  • 15 Pabla R, Weyrich AS, Dixon DA. et al. Integrin-dependent control of translation: Engagement of integrin IIb 3 regulates synthesis of proteins in activated human platelets. J Cell Biol 1999; 144: 175-184.
  • 16 Gnatenko DV, Dunn JJ, McCorkle SR. et al. Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood 2003; 101: 2285-2293.
  • 17 McRedmond JP, Park SD, Reilly DF. et al. Integration of proteomics and genomics in platelets: a profile of platelet proteins and platelet-specific genes. Mol Cell Proteomics 2004; 3: 133-144.
  • 18 Schwabe H, Stein U, Walther W. High-copy cDNA amplification of minimal total RNA quantities for gene expression analysis. Mol Biotechnol 2000; 14: 165-172.
  • 19 Rox JM, Bugert P, Müller J. et al. Gene expression analysis in platelets from a single donor: evaluation of a PCR-based amplification technique. Clin Chem 2004; 50: 2271-2278.
  • 20 Godfrey TE, Kim SH, Chavira M. et al. Quantitative mRNA expression analysis from formalin-fixed, paraffin-embedded tissues using 5’ nuclease quantitative reverse transcription-polymerase chain reaction. J Mol Diagn 2000; 2: 84-91.
  • 21 Zhang F, Wang ZM, Liu HY. et al. Application of RT-PCR in formalin-fixed and paraffin-embedded lung cancer tissues. Acta Pharmacol Sin 2010; 31: 111-117.
  • 22 Shim MH, Hoover A, Blake N. et al. Gene expression profile of primary human CD34+CD38lo cells differentiating along the megakaryocyte lineage. Exp Hematol 2004; 32: 638-648.
  • 23 Morris TD, Weber LA, Hickey E. et al. Changes in the stability of a human H3 histone mRNA during the HeLa cell cycle. Mol Cell Biol 1991; 11: 544-553.
  • 24 Harris ME, Bohni R, Schneiderman MH. et al. Regulation of histone mRNA in the unperturbed cell cycle: Evidence suggesting control at two posttranscriptional steps. Mol. Cell Biol 1991; 11: 2416-2424.
  • 25 Greenberg CS, Sane DC, Lai T. Hemostasis and Thrombosis. 5th edn. Lippincott Williams and Wilkins; Philadelphia: 2006: 153-181.
  • 26 Varga-Szabo D, Pleines I, Nieswandt B. Cell adhesion mechanisms in platelets. Ar- terioscler Thromb Vasc Biol 2008; 28: 403-412.
  • 27 Luo SZ. Role of the transmembrane domain of glycoprotein IX in assembly of the glycoprotein Ib-IX complex. J Thromb Haemost 2007; 5: 2494-2502.
  • 28 Preston RJ, Tran S, Johnson JA. et al. Platelet factor 4 impairs the anticoagulant activity of activated protein C. Biol Chem 2009; 284: 5869-5875.
  • 29 Pruissen DM, Slooter AJ, Rosendaal FR. et al. Coagulation factor XIII gene variation, oral contraceptives, and risk of ischemic stroke. Blood 2008; 111: 1282-1286.
  • 30 Muszbek L, Yee VC, Hevessy Z. Blood coagulation factor XIII: structure and function. Thromb Res 1999; 94: 271-305.
  • 31 Poon MC, Russel JA, Low S. et al. Hemopoietic origin of factor XIII subunits in platelets, monocytes and plasma. Evidence from bone marrow transplantation studies. J Clin Invest 1989; 84: 787-792.
  • 32 Wolpl A, Lattke H, Board PG. et al. Coagulation factor XIII A and B subunits in bone marrow and liver transplantation. Transplantation 1987; 43: 151-153.
  • 33 Joist JH, Niewiarowski S. Retention of platelet fibrin stabilizing factor during the platelet release reaction and clot retraction. Thromb Diath Haemorrh 1973; 29: 679-683.
  • 34 Adany R, Bardos H. Factor XIII subunit A as an intracellular transglutaminase. Cell Mol Life Sci 2003; 60: 1049-1060.
  • 35 Kaetsu H, Hashiguchi T, Foster D. et al. Expression and release of the a and b subunits for human coagulation factor XIII in baby hamster kidney (BHK) cells. J Biochem 1996; 119: 961-969.
  • 36 MacKenzie A, Wilson HL, Kiss-Toth E. et al. Rapid secretion of interleukin-1beta by microvesicle shedding. Immunity 2001; 15: 825-835.
  • 37 Mignatti P, Morimoto T, Rifkin DB. Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex. J Cell Physiol 1992; 151: 81-93.
  • 38 Backhaus R, Zehe C, Wegehingel S. et al. Unconventional protein secretion: membrane translocation of FGF-2 does not require protein unfolding. J Cell Sci 2004; 117: 1727-1736.
  • 39 Cordell PA, Kile BT, Standeven KF. et al. Association of coagulation factor XIII-A with Golgi proteins within monocyte-macrophages: implications for subcellular trafficking and secretion. Blood 2010; 115: 2674-2681.
  • 40 Owen WG, Bichler J, Ericson D. et al. Gating of thrombin in platelet aggregates by pO2-linked lowering of extracellular Ca2+ concentration. Biochemistry 1995; 34: 9277-9281.
  • 41 Jayo A, Conde I, Lastres P. et al. New insights into the expression and role of platelet factor XIII-A. J Thromb Haemost 2009; 7: 1184-1191.
  • 42 Serrano K, Devine DV. Intracellular factor XIII crosslinks platelet cytoskeletal elements upon platelet activation. Thromb Haemost 2002; 88: 315-320.
  • 43 Kasahara K, Souri M, Kaneda M. et al. Impaired clot retraction in factor XIIIA subunit-deficient mice. Blood 2010; 115: 1277-1279.
  • 44 Cohen I, Glaser T, Veis A. et al. Ca2+dependent cross-linking processes in human platelets. Biochim Biophys Acta 1981; 676: 137-147.
  • 45 Muszbek L, Polgar J, Boda Z. Platelet factor XIII becomes active without the release of activation peptide during platelet activation. Thromb Haemost 1993; 69: 282-285.
  • 46 Hornyak TJ, Shafer JA. Role of calcium ion in the generation of factor XIII activity. Biochemistry 1991; 30: 6175-6182.
  • 47 Ando Y, Imamura S, Yamagata Y. et al. Platelet factor XIII is activated by calpain. Biochem Biophys Res Commun 1987; 144: 484-490.
  • 48 Dunois-Larde C, Capron C, Fichelson S. et al. Exposure of human megakaryocytes to high shear rates accelerates platelet production. Blood 2009; 114: 1875-1883
  • 49 Prodan CI, Joseph PM, Vincent AS. et al. Coated-platelets in ischemic stroke: differences between lacunar and cortical stroke. J Thromb Haemost 2008; 6: 609-614.
  • 50 Aksu H, Ozer O, Unal H. et al. Significance of mean platelet volume on prognosis of patients with and without aspirin resistance in settings of non-ST-segment elevated acute coronary syndromes. Blood Coagul Fibrinolysis 2009; 20: 686-693.
  • 51 Wysokinski WE., Konik E, McBane RD. et al. Left Atrial Stasis and VWF- ADAMTS 13 system in atrial fibrillation. J Am Coll Cardiol. 2010 55. (Suppl): Abstract 2505-439 - A213.
  • 52 Li J, Smyth P, Flavin R. et al. Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells. BMC Biotechnol 2007; 7: 36
  • 53 Jarzab M, Rozanowski P, Kowalska M. et al. Optimization of the method of RNA isolation from paraffin blocks to assess gene expression in breast cancer. Pol J Pathol 2008; 59: 85-91.
  • 54 Bibikova M, Talantov D, Chudin E. et al. Quantitative gene expression profiling in formalin-fixed, paraffin-embedded tissues using universal bead arrays. Am J Pathol 2004; 165: 1799-1807.
  • 55 McBane RD, Hodge DO, Wysokinski WE. Clinical and echocardiographic measures governing thromboembolism destination in atrial fibrillation. Thromb Haemost. 2008; 99: 951-955.