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Journal of Thrombosis and Thrombolysis

Erschienen in:

01.08.2010

Human cytomegalovirus increases HUVEC sensitivity to thrombin and modulates expression of thrombin receptors

verfasst von: Milan Popović, Svetlana Paskaš, Maja Živković, Ladislav Burysek, Yves Laumonnier

Erschienen in: Journal of Thrombosis and Thrombolysis | Ausgabe 2/2010

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Abstract

Human cytomegalovirus (HCMV) establishes a life-long persistent infection. HCMV infection could be associated with chronic inflammatory diseases, such as cardiovascular disease and atherosclerosis. Here we observed that in HCMV (AD-169) pre-exposed human umbilical vein endothelial cells (HUVEC), thrombin-induced expression of IL-1α and M-CSF is markedly enhanced compared to the un-exposed cells. Study of the expression of thrombin receptor genes in HUVEC showed that HCMV triggered a time- and concentration-dependent expression of the thrombin receptors PAR1, PAR3 and PAR4 at the mRNA level. Induction of PAR1 and PAR3 mRNA expression is due to transcriptional activation of their promoters as shown by gene reporter assay. Furthermore, the virus induced expression of PAR1 and PAR3 but not PAR4 proteins, as analyzed by Western immunoblotting. However, flow cytometric analysis revealed that only PAR3, expressed at very low level in control HUVEC, is induced at the surface during the exposure to the virus. Our data suggest that although exposure to HCMV induces a minor increase of cell-surface receptors expression, it does make endothelial cells more responsive to additional thrombin stimulation.

Mocarski ES Jr, Shenk T, Pass RF (2007) Cytomegaloviruses. In: Knipe DM, Howley PM (eds) Fields virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 2701–2772

Sorlie PD, Nieto FJ, Adam E, Folsom AR, Shahar E, Massing M (2000) A prospective study of cytomegalovirus, herpes simplex virus 1, and coronary heart disease: the atherosclerosis risk in communities (ARIC) study. Arch Intern Med 160:2027–2032CrossRefPubMed

Qavi HB, Melnick JL, Adam E, Debakey ME (2000) Frequency of coexistence of cytomegalovirus and Chlamydia pneumoniae in atherosclerotic plaques. Cent Eur J Public Health 8:71–73PubMed

Chen R, Xiong S, Yang Y, Fu W, Wang Y, Ge J (2003) The relationship between human cytomegalovirus infection and atherosclerosis development. Mol Cell Biochem 249:91–96CrossRefPubMed

Berencsi K, Endresz V, Klurfeld D, Kari L, Kritchevsky D, Gönczöl E (1998) Early atherosclerotic plaques in the aorta following cytomegalovirus infection of mice. Cell Adhes Commun 5:39–47CrossRefPubMed

Zhou YF, Yu ZX, Wanishsawad C, Shou M, Epstein SE (1999) The immediate early gene products of human cytomegalovirus increase vascular smooth muscle cell migration, proliferation, and expression of PDGF beta-receptor. Biochem Biophys Res Commun 256:608–613CrossRefPubMed

Hsich E, Zhou YF, Paigen B, Johnson TM, Burnett MS, Epstein SE (2001) Cytomegalovirus infection increases development of atherosclerosis in Apolipoprotein-E knockout mice. Atherosclerosis 156:23–28CrossRefPubMed

Burnett MS, Gaydos CA, Madico GE, Glad SM, Paigen B, Quinn TC, Epstein SE (2001) Atherosclerosis in apoE knockout mice infected with multiple pathogens. J Infect Dis 183:226–231CrossRefPubMed

Krebs P, Scandella E, Bolinger B, Engeler D, Miller S, Ludewig B (2007) Chronic immune reactivity against persisting microbial antigen in the vasculature exacerbates atherosclerotic lesion formation. Arterioscler Thromb Vasc Biol 27:2206–2213CrossRefPubMed

10.

Bentz GL, Jarquin-Pardo M, Chan G, Smith MS, Sinzger C, Yurochko AD (2006) Human cytomegalovirus (HCMV) infection of endothelial cells promotes naive monocyte extravasation and transfer of productive virus to enhance hematogenous dissemination of HCMV. J Virol 80:11539–11555CrossRefPubMed

11.

Dengler TJ, Raftery MJ, Werle M, Zimmermann R, Schönrich G (2000) Cytomegalovirus infection of vascular cells induces expression of pro-inflammatory adhesion molecules by paracrine action of secreted interleukin-1beta. Transplantation 69:1160–1168CrossRefPubMed

12.

Streblow DN, Dumortier J, Moses AV, Orloff SL, Nelson JA (2008) Mechanisms of cytomegalovirus-accelerated vascular disease: induction of paracrine factors that promote angiogenesis and wound healing. Curr Top Microbiol Immunol 325:397–415CrossRefPubMed

13.

Viles-Gonzalez JF, Fuster V, Badimon JJ (2005) Thrombin/inflammation paradigms: a closer look at arterial and venous thrombosis. Am Heart J 149(1 Suppl):19–31CrossRef

14.

Bunnett NW (2006) Protease-activated receptors: how proteases signal to cells to cause inflammation and pain. Semin Thromb Hemost 32(Suppl.1):39–48CrossRefPubMed

15.

Jaffe EA, Grulich J, Weksler BB, Hampel G, Watanabe K (1987) Correlation between thrombin-induced prostacyclin production and inositol trisphosphate and cytosolic free calcium levels in cultured human endothelial cells. J Biol Chem 262:8557–8565PubMed

16.

Hallam TJ, Pearson JD, Needham LA (1988) Thrombin-stimulated elevation of human endothelial-cell cytoplasmic free calcium concentration causes prostacyclin production. Biochem J 251:243–249PubMed

17.

Hattori R, Hamilton KK, Fugate RD, McEver RP, Sims PJ (1989) Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem 264:7768–7771PubMed

18.

Rahman A, Anwar KN, True AL, Malik AB (1999) Thrombin-induced p65 homodimer binding to downstream NF-kappa B site of the promoter mediates endothelial ICAM-1 expression and neutrophil adhesion. J Immunol 162:5466–5476PubMed

19.

Bogatcheva NV, Garcia JG, Verin AD (2002) Molecular mechanisms of thrombin-induced endothelial cell permeability. Biochemistry 67:75–84PubMed

20.

Popovic M, Laumonnier Y, Burysek L, Syrovets T, Simmet T (2008) Thrombin-induced expression of endothelial CX3CL1 potentiates monocyte CCL2 production and transendothelial migration. J Leukoc Biol 84:215–223CrossRefPubMed

21.

Coughlin SR (2005) Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost 3:1800–1814CrossRefPubMed

22.

Carney DH, Redin W, McCroskey L (1992) Role of high-affinity thrombin receptors in postclotting cellular effects of thrombin. Semin Thromb Hemost 18:91–103CrossRefPubMed

23.

Ishihara H, Connolly AJ, Zeng D, Kahn ML, Zheng YW, Timmons C, Tram T, Coughlin SR (1997) Protease-activated receptor 3 is a second thrombin receptor in humans. Nature (London) 38:502–506CrossRef

24.

Kahn ML, Zheng YW, Huang W, Bigornia V, Zeng D, Moff S, Farese RV Jr, Tam C, Coughlin SR (1998) A dual thrombin receptor system for platelet activation. Nature (London) 394:690–694CrossRef

25.

O’Brien PJ, Prevost N, Molino M, Hollinger MK, Woolkalis MJ, Woulfe DS, Brass LF (2000) Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1. J Biol Chem 275:13502–13509CrossRefPubMed

26.

Laumonnier Y, Nadaud S, Agrapart M, Soubrier F (2000) Charac-terization of an upstream enhancer region in the promoter of the human endothelial nitric-oxide synthase gene. J Biol Chem 275:40732–40741CrossRefPubMed

27.

Levi M, van der Poll T, Buller HR (2004) Bidirectional relation between inflammation and coagulation. Circulation 109:2698–2704CrossRefPubMed

28.

Gredmark S, Strååt K, Homman-Loudiyi M, Kannisto K, Söderberg-Nauclér C (2007) Human cytomegalovirus downregulates expression of receptors for platelet-derived growth factor by smooth muscle cells. J Virol 81:5112–5120CrossRefPubMed

29.

Strååt K, de Klark R, Gredmark-Russ S, Eriksson P, Söderberg-Nauclér C (2009) Infection with human cytomegalovirus alters the MMP-9/TIMP-1 balance in human macrophages. J Virol 83:830–835CrossRefPubMed

30.

Andreoni KA, Wang X, Huang SM, Huang ES (2002) Human cytomegalovirus hyperimmune globulin not only neutralizes HCMV infectivity, but also inhibits HCMV-induced intracellular NF-kappaB, Sp1, and PI3-K signaling pathways. J Med Virol 67:33–40CrossRefPubMed

31.

Bolovan-Fritts CA, Wiedeman JA (2002) Mapping the viral genetic determinants of endothelial cell tropism in human cytomegalovirus. J Clin Virol 25:S97–S109CrossRefPubMed

32.

Fish KN, Soderberg-Naucler C, Mills LK, Stenglein S, Nelson JA (1998) Human cytomegalovirus persistently infects aortic endothelial cells. J Virol 72:5661–5668PubMed

33.

Bolovan-Fritts CA, Wiedeman JA (2001) Human cytomegalovirus strain Toledo lacks a virus-encoded tropism factor required for infection of aortic endothelial cells. J Infect Dis 184:1252–1261CrossRefPubMed

34.

Simmen KA, Singh J, Luukkonen BG, Lopper M, Bittner A, Miller NE, Jackson MR, Compton T, Fruh K (1999) Global modulation of cellular transcription by human cytomegalovirus is initiated by viral glycoprotein B. Proc Natl Acad Sci USA 98:7140–7145CrossRef

35.

Boyle KA, Pietropaolo RL, Compton T (1999) Engagement of the cellular receptor for glycoprotein B of human cytomegalovirus activates the interferon-responsive pathway. Mol Cell Biol 19:3607–3613PubMed

36.

Boehme KW, Singh J, Perry ST, Compton T (2004) Human cytomegalovirus elicits a coordinated cellular antiviral response via envelope glycoprotein B. J Virol 78:1202–1211CrossRefPubMed

37.

Coughlin SR (2000) Signaling and protease-activated receptors. Nature 407:258–264CrossRefPubMed

38.

Shapiro MJ, Coughlin SR (1998) Separate signals for agonist-independent and agonist-triggered trafficking of protease-activated receptor 1. J Biol Chem 273:29009–29014CrossRefPubMed

39.

Nakanishi-Matsui M, Zheng YW, Sulciner DJ, Weiss EJ, Ludeman MJ, Coughlin SR (2000) PAR3 is a cofactor for PAR4 activation by thrombin. Nature 404:609–613CrossRefPubMed

40.

McLaughlin JN, Patterson MM, Malik AB (2007) Protease-activated receptor-3 (PAR3) regulates PAR1 signaling by receptor dimerization. Proc Natl Acad Sci USA 104:5662–5667CrossRefPubMed

41.

Seminario-Vidal L, Kreda S, Jones L, O’Neal W, Trejo J, Boucher RC, Lazarowski ER (2009) Thrombin promotes release of ATP from lung epithelial cells through coordinated activation of rho- and Ca²⁺-dependent signaling pathways. J Biol Chem 284:20638–20648CrossRefPubMed

42.

Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809CrossRefPubMed

43.

Viles-Gonzalez JF, Fuster V, Badimon JJ (2004) Atherothrombosis: a widespread disease with unpredictable and life-threatening consequences. Eur Heart J 25:1197–1207CrossRefPubMed

44.

Butcher EC (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67:1033–1036CrossRefPubMed

45.

Shyy YJ, Wickham LL, Hagan JP, Hsieh HJ, Hu YL, Telian SH, Valente AL, Sung KL, Chien S (1993) Human monocyte colony-stimulating factor stimulates the gene expression of monocyte chemotactic protein-1 and increases the adhesion of monocytes to endothelial monolayers. J Clin Invest 92:1745–1751CrossRefPubMed

Titel: Human cytomegalovirus increases HUVEC sensitivity to thrombin and modulates expression of thrombin receptors
verfasst von: Milan Popović
Svetlana Paskaš
Maja Živković
Ladislav Burysek
Yves Laumonnier
Publikationsdatum: 01.08.2010
Verlag: Springer US
Erschienen in: Journal of Thrombosis and Thrombolysis / Ausgabe 2/2010
Print ISSN: 0929-5305
Elektronische ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-010-0447-7

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Human cytomegalovirus increases HUVEC sensitivity to thrombin and modulates expression of thrombin receptors

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