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European Heart Journal 1999 20(20):1503-1513; doi:10.1053/euhj.1999.1580
Copyright © 1999 by the European Society of Cardiology.
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Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-{alpha}

L. Cominia, T. Bachettia, L. Agnolettia, G. Gaiaa, S. Curellob, B. Milanesic, M. Volterranid, G. Parrinelloe, C. Ceconib, A. Giordanod, A. Cortif and R. Ferrarig,f1

a Cardiovascular Pathophysiology Research Centre, Heart Failure Unit, ‘Salvatore Maugeri’ Foundation for Care and Research, Gussago, Brescia, Italy
d Division of Cardiology, Heart Failure Unit, ‘Salvatore Maugeri’ Foundation for Care and Research, Gussago, Brescia, Italy
b University of Brescia, Spedali Civili, Brescia, Italy
c Clinical Chemistry Laboratory, Haematology Service, Spedali Civili, Brescia, Italy
e Statistics Department, University of Brescia, Brescia, Italy
f DIBIT, San Raffaele Scientific Institute, Milan, Italy
g University of Ferrara, Ferrara, Italy

revised February 22, 1999; accepted February 24, 1999

Abstract

Aims We studied the induction of monocytic inducible nitric oxide synthase expression and the tumour necrosis factor-{alpha} system in patients with congestive heart failure.

Methods and Results Forty-three congestive heart failure patients and 15 healthy subjects were studied. Antigenic tumour necrosis factor-{alpha} and its soluble receptors, measured by ELISA, were increased in chronic heart failure and the increase was related to the clinical severity of the syndrome (tumour necrosis factor-{alpha} from 8·2±5·2 in NYHA class II to 18·2±7·2 in class III and 26·9±13·2pg.ml–1in class IV, P<0·0001 classes III and IV vs class II; soluble tumour necrosis factor receptor I from 1·0±0·2 in class II to 2·3±1·1 in class III and 5·5±3·2ng.ml–1in class IV, P<0·0001 classes III and IV vs class II; soluble tumour necrosis factor receptor II from 2·7±0·7 in class II to 4·9±1·9 in class III and 8·4±5·0ng.ml–1in class IV, P<0·002 classes III and IV vs class II). Monocytic inducible nitric oxide synthase assessed by Western blot, was expressed only in congestive heart failure patients (13 out of 43). The association among monocytic inducible nitric oxide synthase expression, tumour necrosis factor-{alpha} system activation, neurohormones and other clinical parameters was studied. The univariate logistic regression showed that inducible nitric oxide synthase expression was strictly associated with NYHA class (P<0·05), antigenic tumour necrosis factor-{alpha} (P<0·01) and its soluble receptors (P<0·05). The multivariate analysis showed that antigenic tumour necrosis factor-{alpha} was the only predictor for monocytic inducible nitric oxide synthase expression (P<0·05, RR=2·75, CI 1·34–5·43).

Conclusions Inducible nitric oxide synthase is expressed in circulating monocytes of patients with severe congestive heart failure. This phenomenon is linked to the activation of the tumour necrosis factor-{alpha} system.

Key Words: Congestive heart failure, neurohormones, inducible nitric oxide synthase, tumour necrosis factor-{alpha}, monocytes

f1 Correspondence : Prof. Roberto Ferrari, Ospedale S. Anna, Sezione di Malattie dell'Apparato Respiratorio, Nuove Cliniche IIIopiano, Corso Giovecca 203, 44100 Ferrara, Italy.

References

  1. Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumour necrosis factor in congestive heart failure. N Engl J Med. 1990;323:236–241[Abstract]
  2. Ferrari R, Bachetti T, Confortini R. Tumour necrosis factor soluble receptors in patients with various degrees of congestive heart failure. Circulation. 1995;92:1479–1486[Abstract/Free Full Text]
  3. Katz SD, Rao R, Berman JW. Pathophysiological correlates of increased serum tumour necrosis factor in patients with congestive heart failure. Circulation. 1994;90:12–16[Abstract/Free Full Text]
  4. Kubo SH, Rector TS, Bank AJ, Williams RE, Heifetz SM. Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation. 1991;84:1589–1596[Abstract/Free Full Text]
  5. Katz SD, Biasucci L, Sabba C. Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure. J Am Coll Cardiol. 1992;19:918–925[Abstract]
  6. Habib F, Dutka D, Crossman D, Oakley CM, Cleland JGF. Enhanced basal nitric oxide production in heart failure: another failed counter-regulatory vasodilator mechanism? Lancet. 1994;344:371–373[CrossRef][ISI][Medline]
  7. Yoshizumi M, Perrella MA, Burnett JCJ, Lee M-E. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. Circ Res. 1993;73:205–209[Abstract]
  8. Lamas S, Michel T, Brenner BM, Marsden PA. Nitric oxide synthesis in endothelial cells: evidence for a pathway inducible by TNF-{alpha}. Am J Physiol. 1991;261:C634–C641
  9. Busse R, Mulsch A. Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells. FEBS Lett. 1990;275:87–90[CrossRef][ISI][Medline]
  10. Balligand J-L, Ungureanu-Longrois D, Simmons WW. Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. J Biol Chem. 1994;269:27580–27588[Abstract/Free Full Text]
  11. Drapier J-C, Wietzerbin J, Hibbs JRT. Interferon-{gamma} and tumor necrosis factor induce the L-arginine-dependent cytotoxic effector mechanism in murine macrophages. Eur J Immunol. 1988;18:1587–1592[ISI][Medline]
  12. Hibbs JB Jr. Synthesis of nitric oxide from L-arginine: A recently discovered pathway induced by cytokines with antitumour and antimicrobial activity. Res Immunol. 1991;142:565–569[CrossRef][ISI][Medline]
  13. Eur Heart J. 1997;18:1457–1464[Abstract/Free Full Text]
  14. Ansari A. Syndromes of cardiac cachexia and the cachectic heart: current perspective. Prog Cardiovasc Dis. 1987;30:45–60[CrossRef][ISI][Medline]
  15. Morrison WL, Edwards RHT. Cardiac cachexia. BMJ. 1991;302:301–302[ISI][Medline]
  16. Anand IS, Ferrari R, Kalra GS, Wahi PL, Poole Wilson PA, Harris P. Edema of cardiac origin: studies of body water and sodium, renal function, hemodynamic indexes, and plasma hormones in untreated congestive cardiac failure. Circulation. 1989;80:299–305[Abstract/Free Full Text]
  17. Ceconi C, Condorelli E, Quinzanini M, Rodella A, Ferrari R, Harris P. Noradrenaline, atrial natriuretic peptide, bombesin and neurotensin in myocardium and blood of rats in congestive cardiac failure. Cardiovasc Res. 1989;23:674–682[ISI][Medline]
  18. Poiesi C, Rodella A, Mantero G, Cannella G, Ferrari R, Albertini A. Improved radioimmunoassay of atrial natriuretic peptide in plasma. Clin Chem. 1989;35:1431–1434[Abstract/Free Full Text]
  19. Espevik T, Nissen-Meyer J. A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J Immunol Methods. 1986;95:99–105[CrossRef][ISI][Medline]
  20. Yam LTL, Li CY, Crosby WH. Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol. 1971;55:283–290[ISI][Medline]
  21. Hayhoe FGJ, Quaglino D. Haematological cytochemistry. New York: Churchill, Livingstone; 1980. p. 146–71
  22. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin Phenol Reagent. J Biol Chem. 1951;193:265–275[Free Full Text]
  23. Comini L, Bachetti T, Gaia G. Aorta and skeletal muscle NO-synthase expression in experimental heart failure. J Mol Cell Cardiol. 1996;28:2241–2248[CrossRef][ISI][Medline]
  24. Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979;76:4350–4354[Abstract/Free Full Text]
  25. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, [15N]nitrate in biological fluids. Anal Biochem. 1982;126:131–138[CrossRef][ISI][Medline]
  26. Charles IG, Palmer RMJ, Hickery MS. Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte. Proc Nat Acad Sci U S A. 1993;90:11419–11423[Abstract/Free Full Text]
  27. Nussler AK, Di Silvio M, Billiar TR. Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin. J Exp Med. 1992;176:261–264[Abstract/Free Full Text]
  28. Palmer RM, Hickery MS, Charles IG, Moncada S, Bayliss MT. Induction of nitric oxide synthase in human chondrocytes. Biochem Biophys Res Commun. 1993;193:398–405[CrossRef][ISI][Medline]
  29. Weinberg JB, Misukonis MA, Shami PJ. Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric oxide production by blood monocytes and peritoneal macrophages. Blood. 1995;86:1184–1195[Abstract/Free Full Text]
  30. Padgett EL, Pruett SB. Evaluation of nitrite production by human monocyte-derived macrophages. Biochem Biophys Res Commun. 1992;186:775–781[CrossRef][ISI][Medline]
  31. Schneemann M, Schoedon G, Hofer S, Blau N, Guerrero L, Schaffner A. Nitric oxide synthase is not a constituent of the antimicrobial armature of human mononuclear phagocytes. J Infect Dis. 1993;167:1358–1363[ISI][Medline]
  32. Cameron ML, Granger DL, Weinberg JB, Kozumbo WJ, Koren HS. Human alveolar and peritoneal macrophages mediate fungistasis independently of L-arginine oxidation to nitrite or nitrate. Am Rev Respir Dis. 1990;142:1313–1319[ISI][Medline]
  33. Murray HW, Teitelbaum RF. L-arginine-dependent reactive nitrogen intermediates and the antimicrobial effect of activated human mononuclear phagocytes. J Infect Dis. 1992;165:513–517[ISI][Medline]
  34. Kwon NS, Nathan CF, Stuehr DJ. Reduced biopterin as a cofactor in the generation of nitrogen oxides by murine macrophages. J Biol Chem. 1989;264:20496–20501[Abstract/Free Full Text]
  35. Werner ER, Werner-Felmayer G, Fuchs D, Hausen A, Reibnegger G, Wachter H. Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine 2,3-dioxygenase activity in human cells and cell lines by interferon-gamma. Biochem J. 1989;262:861–866[ISI][Medline]
  36. Denis M. Human monocytes/macrophages: NO or no NO? J Leukoc Biol. 1994;55:682–684[Abstract]
  37. Weiz A, Oguchi S, Cicatiello L, Esumi H. Dual mechanism for the control of inducible-type NO synthase gene expression in macrophages during activation by interferon-{gamma} and bacterial lipopolysaccharide. J Biol Chem. 1994;269:8324–8333[Abstract/Free Full Text]
  38. Fuchs D, Murr C, Reibnegger G. Nitric oxide synthase and antimicrobial armature of human macrophages. J Infect Dis. 1994;84:224–225
  39. Padgett EL, Pruett SB. Rat, mouse and human neutrophils stimulated by a variety of activating agents produce much less nitrite than rodent macrophages. Immunology. 1995;84:135–141[ISI][Medline]
  40. Nathan C, Xie Q-W. Regulation of biosynthesis of nitric oxide. J Biol Chem. 1994;269:13725–13728[Free Full Text]
  41. Jude B, Agraou B, McFadden EP. Evidence for time-dependence activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina. Circulation. 1994;90:1662–1668[Abstract/Free Full Text]
  42. Kalman J, Levine B, Mayer L. Is immune activation a unique feature of idiopathic dilated cardiomyopathy? A study of markers of T-cell and monocyte activation in patients with chronic ischaemic and nonischaemic heart failure (Abstr). Circulation. 1992;86:1–527[Abstract/Free Full Text]
  43. Anker SD, Egerer KR, Volk HD, Kox WJ, Poole-Wilson PA, Coats AJ. Elevated soluble CD 14 receptor and altered cytokines in chronic heart failure. Am J Cardiol. 1997;79:1426–1430[CrossRef][ISI][Medline]
  44. Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann R, Rauchhaus M, Poole-Wilson PA, Coats AJS, Anker SD. Endotoxin and immune activation in chronic heart failure patients with and without peripheral oedema (Abstr). Circulation. 1998;19:174
  45. Fukuchi M, Hussain SNA, Giaid A. Heterogeneous expression and activity of endothelial and inducible nitric oxide synthases in end-stage human heart failure. Their relation to lesion site and ß-adrenergic receptor therapy. Circulation. 1998;98:132–139[Abstract/Free Full Text]
  46. Packer M. Is tumor necrosis factor an important neurohormonal mechanism in chronic heart failure? Circulation. 1995;92:1379–1382[Free Full Text]
  47. Anker SD, Volterrani M, Egerer KR. Tumour necrosis factor alpha as a predictor of impaired peak leg blood flow in patients with chronic heart failure. Q J M. 1998;91:199–203
  48. Meldrum DR. Tumour necrosis factor in the heart. Am J Physiol. 1998;274:R577–R595
  49. Knowles RG, Salter M, Brooks SL, Moncada S. Anti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat. Biochem Biophys Res Comm. 1990;172:1042–1048[CrossRef][ISI][Medline]
  50. Kilbourn RG, Belloni P. Endothelial cell production of nitrogen oxide in response to interferon gamma in combination with tumor necrosis factor, interleukin-1 or endotoxin. J Natl Cancer Inst. 1990;82:772–776[Abstract/Free Full Text]
  51. Fleming I, Gray GA, Schott C, Stoclet JC. Inducible but not constitutive production of nitric oxide by vascular smooth muscle cells. Eur J Pharmacol. 1991;200:375–376[CrossRef][ISI][Medline]
  52. Chartrain NA, Geller DA, Koty PP. Molecular cloning, structure, and chromosomal localization of the human inducible nitric oxide synthase gene. J Biol Chem. 1994;269:6765–6772[Abstract/Free Full Text]
  53. Ferrari R, Agnoletti L, Comini L, Gaia G, Bachetti T, Gorla R, Volterrani M, Curello S. Sera from patients with heart failure induce "in vivo" apoptosis of human endothelial cells (Abstr). J Am Coll Cardiol. 1998;31:372C
  54. Gulick TS, Chung MK, Pieper SJ, Lange LG, Schreiner GF. Interleukin 1 and tumour necrosis factor inhibit cardiac myocyte ß-adrenergic responsiveness. Proc Natl Acad Sci U S A. 1989;86:6753–6757[Abstract/Free Full Text]
  55. Balligand JL, Ungureanu D, Kelly RA. Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium. J Clin Invest. 1993;91:2314–2319[ISI][Medline]
  56. Suzuki H, Wildhirt SM, Dudek RR, Narayan KS, Bailey AH, Bing RJ. Induction of apoptosis in myocardial infarction and its possible relationship to nitric oxide synthase in macrophages. Tissue & Cell. 1996;28:89–97[CrossRef][ISI][Medline]

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