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Thromb Haemost 1998; 79(01): 217-221
DOI: 10.1055/s-0037-1614242
Review Article
Schattauer GmbH

Lysophosphatidylcholine Decreases the Synthesis of Tissue Factor Pathway Inhibitor in Human Umbilical Vein Endothelial Cells

Naoaki Sato   *
From the National Cardiovascular Center Research Institute, Suita, Osaka, Japan
,
Koichi Kokame
From the National Cardiovascular Center Research Institute, Suita, Osaka, Japan
,
Toshiyuki Miyata
From the National Cardiovascular Center Research Institute, Suita, Osaka, Japan
,
Hisao Kato
From the National Cardiovascular Center Research Institute, Suita, Osaka, Japan
› Author Affiliations
Further Information

Publication History

Received 13 May 1997

Accepted after resubmission 20 August 1997

Publication Date:
08 December 2017 (online)

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Summary

Thrombotic complications are frequently associated with atherosclerosis. Lysophosphatidylcholine (LPC), a component accumulated in oxidatively modified LDL (ox-LDL), is known to play a crucial role in the initiation and progression of atherosclerotic vascular lesions. Since a vascular anticoagulant, tissue factor pathway inhibitor (TFPI), has the function of regulating the initial reaction of tissue factor (TF)-induced coagulation, we investigated the effect of LPC on TFPI synthesis in cultured human umbilical vein endothelial cells (HUVEC). The treatment of HUVEC with LPC for 24 h decreased TFPI antigen levels in both the culture medium and the cell lysate in a dose-dependent manner. Northern blot analysis revealed that LPC caused a time-dependent decrease in the TFPI mRNA levels. The levels of TFPI antigen and mRNA were decreased to 72% and 38%, respectively, by the incubation with 50 μM LPC for 24 h. The down-regulation by LPC of TFPI mRNA expression was not observed in the presence of cycloheximide, suggesting that protein synthesis was involved in the suppression of TFPI mRNA expression. The TFPI mRNA levels in actinomycin D-treated cells were relatively stable, indicating that the down-regulation of TFPI mRNA by LPC would be partly explained by the enhanced mRNA destabilization. In contrast to the significant down-regulatory effects of LPC on TFPI expression, LPC did not induce TF mRNA expression in HUVEC. These results indicate that LPC accumulated in the atherosclerotic vascular wall would suppress endothelial TFPI synthesis, reducing the antithrombotic property of endothelial cells.

* Present address: Dr. N. Sato, First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan


 

  • References

  • 1 Nemerson Y. Tissue factor and hemostasis. Blood. 1988; 71: 1-8.
    PubMedGoogle Scholar
  • 2 Broze Jr GJ, Girard TJ, Novotny WF. Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry. 1990; 29: 7539-46.
    CrossrefPubMedGoogle Scholar
  • 3 Rapaport SI. The extrinsic pathway inhibitor: a regulation of tissue factor-dependent blood coagulation. Thromb Haemost 1991; 66: 6-15.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Wun TC, Kretzmer KK, Girard TJ, Miletich JP, Broze Jr. GJ. Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains. J Biol Chem. 1988; 263: 6001-4.
    PubMedGoogle Scholar
  • 5 Girard TJ, Warren LA, Novotny WF, Bejcek BE, Miletich JP, Broze Jr. GJ. Identification of the 1.4 kb and 4.0 kb messages for the lipoprotein associated coagulation inhibitor and expression of the encoded protein. Thromb Res 1989; 55: 37-50.
    CrossrefPubMedGoogle Scholar
  • 6 Girard TJ, Eddy R, Wesselschmidt RL, MacPhail LA, Likert KM, Byers MG, Shows TB, Broze GJ. Jr. Structure of the human lipoprotein-associated coagulation inhibitor gene, Intron/exon gene organization and localization of the gene to chromosome 2. J Biol Chem 1991; 266: 5036-41.
    PubMedGoogle Scholar
  • 7 van der Logt CPE, Reitsma PH, Bertina RM. Intron-exon organization of human gene coding for the lipoprotein-associated coagulation inhibitor: The factor Xa dependent inhibitor of the extrinsic pathway of coagulation. Biochemistry 1991; 30: 1571-7.
    CrossrefPubMedGoogle Scholar
  • 8 Enjyoji K, Emi M, Mukai T, Imada M, Leppert ML, Lalouel JM, Kato H. Human tissue factor pathway inhibitor (TFPI) gene: Complete genomic structure and localization on the genetic map of chromosome 2q. Genomics 1993; 17: 423-8.
    CrossrefPubMedGoogle Scholar
  • 9 Kokawa T, Abumiya T, Kimura T, Harada-Shiba M, Koh H, Tsushima M, Yamamoto A, Kato H. Tissue factor pathway inhibitor activity in human plasma. Measurement of lipoprotein-associated and free forms in hyperlipidemia. Arterioscler Thromb Vasc Biol 1995; 15: 504-10.
    CrossrefPubMedGoogle Scholar
  • 10 Kokawa T, Enjyoji K, Kumeda K, Kamikubo Y, Harada-Shiba M, Koh H, Tsushima M, Yamamoto A, Kato H. Measurement of the free form of TFPI antigen in hyperlipidemia. Relationship between free and endothelial cell-associated forms of TFPI. Arterioscler Thromb Vasc Biol 1996; 16: 802-8.
    CrossrefPubMedGoogle Scholar
  • 11 Ross R. The pathogenesis of atherosclerosis; a perspective for 1990s. Nature. 1993; 362: 801-9.
    CrossrefPubMedGoogle Scholar
  • 12 Holvoet P, Collen D. Oxidized lipoproteins in atherosclerosis and thrombosis. FASEB J 1994; 8: 1279-84.
    CrossrefPubMedGoogle Scholar
  • 13 Quinn MT, Parthasarathy S, Steinberg D. Lysophosphatidylcholine: A chemotactic factor for human monocytes and its potential role in atherogenesis. Proc Natl Acad Sci USA 1988; 85: 2805-9.
    CrossrefPubMedGoogle Scholar
  • 14 Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD. Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature 1990; 344: 160-2.
    CrossrefPubMedGoogle Scholar
  • 15 Sakai M, Miyazaki A, Hakamata H, Sasaki T, Yui S, Yamazaki M, Shichiri M, Horiuchi S. Lysophosphatidylcholine plays an essential role in the mitogenic effect of oxidized low density lipoprotein on murine macrophages. J Biol Chem 1994; 269: 31430-5.
    PubMedGoogle Scholar
  • 16 Kume N, Cybulsky MI, Gimbrone Jr. MA. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest. 1992; 90: 1138-44.
    CrossrefPubMedGoogle Scholar
  • 17 Kume N, Gimbrone Jr. MA. Lysophosphatidylcholine transcriptionally induces growth factor gene expression in cultured human endothelial cells. J Clin Invest 1994; 93: 907-11.
    CrossrefPubMedGoogle Scholar
  • 18 Zembowicz A, Jones SL, Wu KK. Induction of cyclooxygenase-2 in human umbilical vein endothelial cells by lysophosphatidylcholine. J Clin Invest 1995; 96: 1688-92.
    CrossrefPubMedGoogle Scholar
  • 19 Zembowicz A, Tang J, Wu KK. Transcriptional induction of endothelial nitric oxide synthase type III by lysophosphatidylcholine. J Biol Chem 1995; 270: 17006-10.
    CrossrefPubMedGoogle Scholar
  • 20 Weis JR, Pitas RE, Wilson BD, Rodgers GM. Oxidized low-density lipoprotein increases cultured human endothelial cell tissue factor activity and reduces protein C activation. FASEB J 1991; 5: 2459-65.
    CrossrefPubMedGoogle Scholar
  • 21 Fei H, Berliner JA, Parhami F, Drake TA. Regulation of endothelial cell tissue factor expression by minimally oxidized LDL and lipopolysaccharide. Arterioscler Thromb 1993; 13: 1711-17.
    CrossrefPubMedGoogle Scholar
  • 22 Brand K, Banka CL, Mackman N, Terkeltaub RA, Fan ST, Curtiss LK. Oxidized LDL enhanced lipopolysaccharide-induced tissue factor expression in human adherent monocytes. Arterioscler Thromb 1994; 14: 790-7.
    CrossrefPubMedGoogle Scholar
  • 23 Ishii H, Kizaki K, Horie S, Kazama M. Oxidized low density lipoprotein reduces thrombomodulin transcription in cultured human endothelial cells through degradation of the lipoprotein in lysosomes. J Biol Chem 1996; 271: 8458-65.
    CrossrefPubMedGoogle Scholar
  • 24 Kugiyama K, Sakamoto T, Misumi I, Sugiyama S, Ohgushi M, Ogawa H, Horiguchi M, Yasue H. Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells. Circ Res 1993; 73: 335-43.
    CrossrefPubMedGoogle Scholar
  • 25 Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1988; 85: 2805-9.
    CrossrefPubMedGoogle Scholar
  • 26 Kato K, Elsayed YA, Namoto M, Nakagawa K, Sueishi K. Enhanced expression of tissue factor activity in the atherosclerotic aortas of cholesterol-fed rabbits. Thromb Res 1996; 82: 335-47.
    CrossrefPubMedGoogle Scholar
  • 27 Rana SV, Reimers HJ, Pathikonda MS, Bajaj SP. Expression of tissue factor and factor VIIa/tissue factor inhibitor activity in endotoxin or phorbol ester stimulated U937 monocyte-like cells. Blood 1988; 71: 259-62.
    PubMedGoogle Scholar
  • 28 Ameri A, Kuppuswamy MN, Basu S, Bajaj SP. Expression of tissue factor pathway inhibitor by cultured endothelial cells in response to inflammatory mediators. Blood 1992; 79: 3219-26.
    PubMedGoogle Scholar
  • 29 van der Logt CPE, Dirven RJ, Reitsma PH, Bertina RM. Expression of tissue factor and tissue factor pathway inhibitor in monocytes in response to bacterial lipopolysaccharide and phorbolester. Blood Coagul Fibrinolys 1994; 5: 211-20.
    PubMedGoogle Scholar
  • 30 Kokame K, Kato H, Miyata T. Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes. J Biol Chem 1996; 271: 29659-65.
    CrossrefPubMedGoogle Scholar
  • 31 Enjyoji K, Miyata T, Kamikubo Y, Kato H. Effect of heparin on the inhibition of factor Xa by tissue factor pathway inhibitor: a segment, Gly212-Phe243, of the third Kunitz domain is a heparin-binding site. Biochemistry 1995; 34: 5725-35.
    CrossrefPubMedGoogle Scholar
  • 32 Shigematsu Y, Miyata T, Higashi S, Miki T, Sadler JE, Iwanaga S. Expression of human soluble tissue factor in yeast and enzymatic properties of its complex with factor VIIa. J Biol Chem 1992; 267: 21329-37.
    PubMedGoogle Scholar
  • 33 Scarpati EM, Wen D, Broze Jr GJ, Miletich JP, Flandermeyer RR, Siegel NR, Sadler JE. Human tissue factor: cDNA sequence and chromosome localization of the gene. Biochemistry 1987; 26: 5234-8.
    CrossrefPubMedGoogle Scholar
  • 34 Mackman N. Regulation of tissue factor. FASEB J 1995; 9: 883-9.
    CrossrefPubMedGoogle Scholar
  • 35 Lee ME, Temizer DH, Clifford JA, Quertermous T. Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells. J Biol Chem 1991; 266: 16188-92.
    PubMedGoogle Scholar
  • 36 Jougasaki M, Kugiyama K, Saito Y, Nakao K, Imura H, Yasue H. Suppression of endothelin-1 secretion by lysophosphatidylcholine in oxidized low density lipoprotein in cultured vascular endothelial cells. Circ Res 1992; 71: 614-9.
    CrossrefPubMedGoogle Scholar
  • 37 Abumiya T, Yamaguchi T, Terasaki T, Kokawa T, Kario K, Kato H. Decreased plasma tissue factor pathway inhibitor activity in ischemic stroke patients. Thromb Haemost 1995; 74: 1050-4.
    Article in Thieme ConnectPubMedGoogle Scholar