Pharmacological inhibition of phospholipase D protects mice from occlusive thrombus formation and ischemic stroke-brief report

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 33, Issue 9, 2013, Pages 2212-2217

  Stegner, David ^a   Thielmann, Ina ^a   Kraft, Peter ^a   Frohman, Michael A ^b   Stoll, Guido ^a   Nieswandt, Bernhard ^a  

^a UNIVERSITY HOSPITAL WÜRZBURG   (Germany)

^b STONY BROOK UNIVERSITY   (United States)

Author keywords

5 fluoro 2 indolyl des chlorohalopemide; cerebral stroke; phospholipase D; thrombosis

Indexed keywords

PHOSPHOLIPASE D;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD CLOTTING; BRAIN ISCHEMIA; CONTROLLED STUDY; MIDDLE CEREBRAL ARTERY OCCLUSION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTECTION; THROMBOCYTE ACTIVATION; THROMBOSIS;

5-FLUORO-2-INDOLYL DES-CHLOROHALOPEMIDE; CEREBRAL STROKE; PHOSPHOLIPASE D; THROMBOSIS;

ANIMALS; BLOOD PLATELETS; CAROTID ARTERY DISEASES; DISEASE MODELS, ANIMAL; DOMPERIDONE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; FIBRINOLYTIC AGENTS; HEMOSTASIS; INDOLES; INFARCTION, MIDDLE CEREBRAL ARTERY; INTEGRINS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; PHOSPHOLIPASE D; RECOVERY OF FUNCTION; THROMBOSIS; TIME FACTORS;

EID: 84883277833     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.113.302030     Document Type: Article

References (28)

1. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006;367:1747-1757. (Pubitemid 43767064)
2. Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and casefatality in the late 20th century. Lancet Neurol. 2003;2:43-53. (Pubitemid 37443343)
3. Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood. 2008;112:3555-3562.
4. Adams HP Jr, Effron MB, Torner J, Dávalos A, Frayne J, Teal P, Leclerc J, Oemar B, Padgett L, Barnathan ES, Hacke W; AbESTT-II Investigators. Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II). Stroke. 2008;39:87-99.
5. Kleinschnitz C, De Meyer SF, Schwarz T, Austinat M, Vanhoorelbeke K, Nieswandt B, Deckmyn H, Stoll G. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood. 2009;113:3600-3603.
6. Stegner D, Nieswandt B. Platelet receptor signaling in thrombus formation. J Mol Med (Berl). 2011;89:109-121.
7. Kleinschnitz C, Pozgajova M, Pham M, Bendszus M, Nieswandt B, Stoll G. Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation. 2007;115:2323-2330. (Pubitemid 46685900)
8. McDermott M, Wakelam MJ, Morris AJ. Phospholipase D. Biochem Cell Biol. 2004;82:225-253. (Pubitemid 38580885)
9. Vorland M, Holmsen H. Phospholipase D in human platelets: presence of isoenzymes and participation of autocrine stimulation during thrombin activation. Platelets. 2008;19:211-224. (Pubitemid 351574443)
10. Jenkins GM, Frohman MA. Phospholipase D: a lipid centric review. Cell Mol Life Sci. 2005;62:2305-2316. (Pubitemid 41500546)
11. Thielmann I, Stegner D, Kraft P, Hagedorn I, Krohne G, Kleinschnitz C, Stoll G, Nieswandt B. Redundant functions of phospholipases d1 and d2 in platelet alpha-granule release. J Thromb Haemost. 2012;10:2361-2372.
12. Elvers M, Stegner D, Hagedorn I, Kleinschnitz C, Braun A, Kuijpers ME, Boesl M, Chen Q, Heemskerk JW, Stoll G, Frohman MA, Nieswandt B. Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1. Sci Signal. 2010;3:ra1.
13. Peng X, Frohman MA. Mammalian phospholipase D physiological and pathological roles. Acta Physiol (Oxf). 2012;204:219-226.
14. Su W, Yeku O, Olepu S, Genna A, Park JS, Ren H, Du G, Gelb MH, Morris AJ, Frohman MA. 5-Fluoro-2-indolyl des-chlorohalopemide (FIPI), a phospholipase D pharmacological inhibitor that alters cell spreading and inhibits chemotaxis. Mol Pharmacol. 2009;75:437-446.
15. Sato T, Hongu T, Sakamoto M, Funakoshi Y, Kanaho Y. Molecular mechanisms of N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation and degranulation in mouse neutrophils: phospholipase D is dispensable. Mol Cell Biol. 2013;33:136-145.
16. Su W, Chen Q, Frohman MA. Targeting phospholipase D with small-molecule inhibitors as a potential therapeutic approach for cancer metastasis. Future Oncol. 2009;5:1477-1486.
17. Monovich L, Mugrage B, Quadros E, Toscano K, Tommasi R, LaVoie S, Liu E, Du Z, LaSala D, Boyar W, Steed P. Optimization of halopemide for phospholipase D2 inhibition. Bioorg Med Chem Lett. 2007;17:2310-2311. (Pubitemid 46484301)
18. Ali WH, Chen Q, Delgiorno KE, Su W, Hall JC, Hongu T, Tian H, Kanaho Y, Di Paolo G, Crawford HC, Frohman MA. Deficiencies of the lipid-signaling enzymes phospholipase D1 and D2 alter cytoskeletal organization, macrophage phagocytosis, and cytokine-stimulated neutrophil recruitment. PLoS One. 2013;8:e55325.
19. Nishikimi A, Fukuhara H, Su W, et al. Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science. 2009;324:384-387.
20. Dall'Armi C, Hurtado-Lorenzo A, Tian H, Morel E, Nezu A, Chan RB, Yu WH, Robinson KS, Yeku O, Small SA, Duff K, Frohman MA, Wenk MR, Yamamoto A, Di Paolo G. The phospholipase D1 pathway modulates macroautophagy. Nat Commun. 2010;1:142.
21. Monovich L, Mugrage B, Quadros E, Toscano K, Tommasi R, LaVoie S, Liu E, Du Z, LaSala D, Boyar W, Steed P. Optimization of halopemide for phospholipase D2 inhibition. Bioorg Med Chem Lett. 2007;17:2310-2311. (Pubitemid 46484301)
22. Loonen AJ, Soudijn W. Halopemide, a new psychotropic agent. Cerebral distribution and receptor interactions. Pharm Weekbl Sci. 1985;7:1-9. (Pubitemid 15125256)
23. Chen Q, Hongu T, Sato T, Zhang Y, Ali W, Cavallo JA, van der Velden A, Tian H, Di Paolo G, Nieswandt B, Kanaho Y, Frohman MA. Key roles for the lipid signaling enzyme phospholipase d1 in the tumor microenvironment during tumor angiogenesis and metastasis. Sci Signal. 2012;5:ra79.
24. Braun A, Varga-Szabo D, Kleinschnitz C, Pleines I, Bender M, Austinat M, Bösl M, Stoll G, Nieswandt B. Orai1 (CRACM1) is the platelet SOC channel and essential for pathological thrombus formation. Blood. 2009;113:2056-2063.
25. Rodgers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemost. 1990;16:1-20. (Pubitemid 20049639)
26. Caro JJ, Huybrechts KF, Duchesne I. Management patterns and costs of acute ischemic stroke: an international study. For the Stroke Economic Analysis Group. Stroke. 2000;31:582-590. (Pubitemid 30131640)
27. Kellert L, Hametner C, Rohde S, Bendszus M, Hacke W, Ringleb P, Stampfl S. Endovascular stroke therapy: tirofiban is associated with risk of fatal intracerebral hemorrhage and poor outcome. Stroke. 2013;44:1453-1455.
28. O'Reilly MC, Scott SA, Brown KA, Oguin TH 3rd, Thomas PG, Daniels JS, Morrison R, Brown HA, Lindsley CW. Development of dual PLD1/2 and PLD2 selective inhibitors from a common 1,3,8-Triazaspiro[4.5]decane Core: discovery of Ml298 and Ml299 that decrease invasive migration in U87-MG glioblastoma cells. J Med Chem. 2013;56:2695-2699.