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01-03-2018 | Original Contribution

Phosphorylation of vasodilator-stimulated phosphoprotein contributes to myocardial ischemic preconditioning

Authors: David Köhler, Sofia-Iris Bibli, Lothar P. Klammer, Judith M. Roth, Rainer Lehmann, Ingrid Fleming, Tiago F. Granja, Andreas Straub, Peter M. Benz, Peter Rosenberger

Published in: Basic Research in Cardiology | Issue 2/2018

Abstract

Ischemic preconditioning (IP) is a well-known strategy to protect organs against cell death following ischemia. The previous work has shown that vasodilator-stimulated phosphoprotein (VASP) is involved in cytoskeletal reorganization and that it holds significant importance for the extent of myocardial ischemia reperfusion injury. Yet, the role of VASP during myocardial IP is, to date, not known. We report here that VASP phosphorylation at serine¹⁵⁷ and serine²³⁹ is induced during hypoxia in vitro and during IP in vivo. The preconditioning-induced VASP phosphorylation inactivates the GP IIb/IIIa integrin receptor on platelets, which results in the reduced formation of organ compromising platelet neutrophil complexes. Experiments in chimeric mice confirmed the importance of VASP phosphorylation during myocardial IP. When studying this in VASP^−/− animals and in an isolated heart model, we were able to confirm the important role of VASP on myocardial IP. In conclusion, we were able to show that IP-induced VASP phosphorylation in platelets is a protective mechanism against the deleterious effects of ischemia.

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Bachmann C, Fischer L, Walter U, Reinhard M (1999) The EVH2 domain of the vasodilator-stimulated phosphoprotein mediates tetramerization, F-actin binding, and actin bundle formation. J Biol Chem 274:23549–23557CrossRefPubMed

Bennett JS, Zigmond S, Vilaire G, Cunningham ME, Bednar B (1999) The platelet cytoskeleton regulates the affinity of the integrin alpha(IIb)beta(3) for fibrinogen. J Biol Chem 274:25301–25307CrossRefPubMed

Benz PM, Blume C, Moebius J, Oschatz C, Schuh K, Sickmann A, Walter U, Feller SM, Renne T (2008) Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. J Cell Biol 180:205–219. https://doi.org/10.1083/jcb.200709181 CrossRefPubMedPubMedCentral

Benz PM, Blume C, Seifert S, Wilhelm S, Waschke J, Schuh K, Gertler F, Munzel T, Renne T (2009) Differential VASP phosphorylation controls remodeling of the actin cytoskeleton. J Cell Sci 122:3954–3965. https://doi.org/10.1242/jcs.044537 CrossRefPubMedPubMedCentral

Bibli SI, Zhou Z, Zukunft S, Fisslthaler B, Andreadou I, Szabo C, Brouckaert P, Fleming I, Papapetropoulos A (2017) Tyrosine phosphorylation of eNOS regulates myocardial survival after an ischaemic insult: role of PYK2. Cardiovasc Res. https://doi.org/10.1093/cvr/cvx058 PubMed

Cohen MV, Yang XM, White J, Yellon DM, Bell RM, Downey JM (2016) Cangrelor-mediated cardioprotection requires platelets and sphingosine phosphorylation. Cardiovasc Drugs Ther 30:229–232. https://doi.org/10.1007/s10557-015-6633-2 CrossRefPubMed

Eckle T, Grenz A, Kohler D, Redel A, Falk M, Rolauffs B, Osswald H, Kehl F, Eltzschig HK (2006) Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice. Am J Physiol Heart Circ Physiol 291:H2533–H2540. https://doi.org/10.1152/ajpheart.00472.2006 CrossRefPubMed

Ferron F, Rebowski G, Lee SH, Dominguez R (2007) Structural basis for the recruitment of profilin-actin complexes during filament elongation by Ena/VASP. EMBO J 26:4597–4606. https://doi.org/10.1038/sj.emboj.7601874 CrossRefPubMedPubMedCentral

Fishbein MC, Meerbaum S, Rit J, Lando U, Kanmatsuse K, Mercier JC, Corday E, Ganz W (1981) Early phase acute myocardial infarct size quantification: validation of the triphenyl tetrazolium chloride tissue enzyme staining technique. Am Heart J 101:593–600CrossRefPubMed

10.

Freynhofer MK, Brozovic I, Bruno V, Farhan S, Vogel B, Jakl G, Willheim M, Hubl W, Wojta J, Huber K (2011) Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events. Thromb Haemost 106:230–239. https://doi.org/10.1160/TH11-02-0077 CrossRefPubMed

11.

Geiger J, Teichmann L, Grossmann R, Aktas B, Steigerwald U, Walter U, Schinzel R (2005) Monitoring of clopidogrel action: comparison of methods. Clin Chem 51:957–965. https://doi.org/10.1373/clinchem.2004.047050 CrossRefPubMed

12.

Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD (1996) Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94:2193–2200CrossRefPubMed

13.

Hart ML, Much C, Gorzolla IC, Schittenhelm J, Kloor D, Stahl GL, Eltzschig HK (2008) Extracellular adenosine production by ecto-5′-nucleotidase protects during murine hepatic ischemic preconditioning. Gastroenterology 135(1739–1750):e1733. https://doi.org/10.1053/j.gastro.2008.07.064

14.

Hausenloy DJ, Garcia-Dorado D, Botker HE, Davidson SM, Downey J, Engel FB, Jennings R, Lecour S, Leor J, Madonna R, Ovize M, Perrino C, Prunier F, Schulz R, Sluijter JPG, Van Laake LW, Vinten-Johansen J, Yellon DM, Ytrehus K, Heusch G, Ferdinandy P (2017) Novel targets and future strategies for acute cardioprotection: position paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart. Cardiovasc Res 113:564–585. https://doi.org/10.1093/cvr/cvx049 CrossRefPubMed

15.

Hauser W, Knobeloch KP, Eigenthaler M, Gambaryan S, Krenn V, Geiger J, Glazova M, Rohde E, Horak I, Walter U, Zimmer M (1999) Megakaryocyte hyperplasia and enhanced agonist-induced platelet activation in vasodilator-stimulated phosphoprotein knockout mice. Proc Natl Acad Sci USA 96:8120–8125CrossRefPubMedPubMedCentral

16.

Heusch G (2015) Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 116:674–699. https://doi.org/10.1161/CIRCRESAHA.116.305348 CrossRefPubMed

17.

Heusch G (2013) Remote conditioning: the future of cardioprotection? J Cardiovasc Med (Hagerstown) 14:176–179. https://doi.org/10.2459/JCM.0b013e328358e507 CrossRef

18.

Heusch G (2015) Treatment of myocardial ischemia/reperfusion injury by ischemic and pharmacological postconditioning. Compr Physiol 5:1123–1145. https://doi.org/10.1002/cphy.c140075 CrossRefPubMed

19.

Holt MR, Critchley DR, Brindle NP (1998) The focal adhesion phosphoprotein, VASP. Int J Biochem Cell Biol 30:307–311CrossRefPubMed

20.

Horstrup K, Jablonka B, Honig-Liedl P, Just M, Kochsiek K, Walter U (1994) Phosphorylation of focal adhesion vasodilator-stimulated phosphoprotein at Ser157 in intact human platelets correlates with fibrinogen receptor inhibition. Eur J Biochem 225:21–27CrossRefPubMed

21.

Kawamura T, Nara N, Kadosaki M, Inada K, Endo S (2000) Prostaglandin E1 reduces myocardial reperfusion injury by inhibiting proinflammatory cytokines production during cardiac surgery. Crit Care Med 28:2201–2208CrossRefPubMed

22.

Kitakaze M, Asakura M, Kim J, Shintani Y, Asanuma H, Hamasaki T, Seguchi O, Myoishi M, Minamino T, Ohara T, Nagai Y, Nanto S, Watanabe K, Fukuzawa S, Hirayama A, Nakamura N, Kimura K, Fujii K, Ishihara M, Saito Y, Tomoike H, Kitamura S, J-WIND Investigators (2007) Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials. Lancet 370:1483–1493. https://doi.org/10.1016/S0140-6736(07)61634-1 CrossRefPubMed

23.

Kohler D, Birk P, Konig K, Straub A, Eldh T, Morote-Garcia JC, Rosenberger P (2011) Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia–reperfusion injury. PLoS One 6:e29494. https://doi.org/10.1371/journal.pone.0029494 CrossRefPubMedPubMedCentral

24.

Kohler D, Straub A, Weissmuller T, Faigle M, Bender S, Lehmann R, Wendel HP, Kurz J, Walter U, Zacharowski K, Rosenberger P (2011) Phosphorylation of vasodilator-stimulated phosphoprotein prevents platelet–neutrophil complex formation and dampens myocardial ischemia–reperfusion injury. Circulation 123:2579–2590. https://doi.org/10.1161/CIRCULATIONAHA.110.014555 CrossRefPubMed

25.

Lee HT, Emala CW (2002) Preconditioning and adenosine protect human proximal tubule cells in an in vitro model of ischemic injury. J Am Soc Nephrol 13:2753–2761CrossRefPubMed

26.

Morel O, Bernhard N, Desprez D, Grunebaum L, Freyssinet JM, Toti F, Bareiss P (2008) Residual prothrombotic status in low responder patients to clopidogrel identified by vasodilator-stimulated phosphoprotein phosphorylation (VASP) analysis? Thromb Haemost 99:448–451. https://doi.org/10.1160/TH07-10-0647 PubMed

27.

Morel O, Viellard C, Faure A, Jesel L, Ohlmann P, Desprez D, Chauvin M, Roul G, Grunebaum L, Bareiss P (2007) Platelet responsiveness to clopidogrel in patients with coronary syndrome. Comparison of platelet aggregation induced by ADP and flow cytometric analysis of intraplatelet VASP phosphorylation. Ann Cardiol Angeiol (Paris) 56:21–29. https://doi.org/10.1016/j.ancard.2006.11.005 CrossRef

28.

Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136CrossRefPubMed

29.

Rosenberger P, Schwab JM, Mirakaj V, Masekowsky E, Mager A, Morote-Garcia JC, Unertl K, Eltzschig HK (2009) Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia. Nat Immunol 10:195–202. https://doi.org/10.1038/ni.1683 CrossRefPubMed

30.

Stazi A, Scalone G, Laurito M, Milo M, Pelargonio G, Narducci ML, Parrinello R, Figliozzi S, Bencardino G, Perna F, Lanza GA, Crea F (2014) Effect of remote ischemic preconditioning on platelet activation and reactivity induced by ablation for atrial fibrillation. Circulation 129:11–17. https://doi.org/10.1161/CIRCULATIONAHA.113.005336 CrossRefPubMed

31.

Straub A, Krajewski S, Hohmann JD, Westein E, Jia F, Bassler N, Selan C, Kurz J, Wendel HP, Dezfouli S, Yuan Y, Nandurkar H, Jackson S, Hickey MJ, Peter K (2011) Evidence of platelet activation at medically used hypothermia and mechanistic data indicating ADP as a key mediator and therapeutic target. Arterioscler Thromb Vasc Biol 31:1607–1616. https://doi.org/10.1161/ATVBAHA.111.226373 CrossRefPubMed

32.

Uhl L, Assmann SF, Hamza TH, Harrison RW, Gernsheimer T, Slichter SJ (2017) Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood 130:1247–1258. https://doi.org/10.1182/blood-2017-01-757930 CrossRefPubMed

33.

Walter U, Gambaryan S (2009) cGMP and cGMP-dependent protein kinase in platelets and blood cells. Handb Exp Pharmacol 191:533–548. https://doi.org/10.1007/978-3-540-68964-5_23 CrossRef

34.

Weissmuller T, Campbell EL, Rosenberger P, Scully M, Beck PL, Furuta GT, Colgan SP (2008) PMNs facilitate translocation of platelets across human and mouse epithelium and together alter fluid homeostasis via epithelial cell-expressed ecto-NTPDases. J Clin Investig 118:3682–3692. https://doi.org/10.1172/JCI35874 CrossRefPubMedPubMedCentral

35.

Zarbock A, Polanowska-Grabowska RK, Ley K (2007) Platelet–neutrophil-interactions: linking hemostasis and inflammation. Blood Rev 21:99–111. https://doi.org/10.1016/j.blre.2006.06.001 CrossRefPubMed

Title: Phosphorylation of vasodilator-stimulated phosphoprotein contributes to myocardial ischemic preconditioning
Authors: David Köhler
Sofia-Iris Bibli
Lothar P. Klammer
Judith M. Roth
Rainer Lehmann
Ingrid Fleming
Tiago F. Granja
Andreas Straub
Peter M. Benz
Peter Rosenberger
Publication date: 01-03-2018
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 2/2018
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-018-0667-0

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