Copyright © 2002 by the European Society of Cardiology.
Plasma tumour necrosis factor-
and early carotid atherosclerosis in healthy middle-aged men
a The Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden
c The Department of Cardiology, Karolinska Hospital, Stockholm, Sweden
e The Cardiovascular Laboratory, the Department of Medicine, Karolinska Hospital, Stockholm, Sweden
f The Institute of Environmental Medicine, Division of Cardiovascular Epidemiology, Karolinska Institute, Stockholm, Sweden
b The Wallenberg Laboratory, Department of Medicine, University of Lund, Malmö University Hospital, Malmö, Sweden
d Division of Ultrasound Research, Wake Forest University School of Medicine, Winston-Salem, NC, U.S.A.
revised May 1, 2001; accepted June 1, 2001
Abstract
Aims Tumour necrosis factor-
(TNF-
) is a proinflammatory cytokine, which is implicated in some metabolic disorders and may play a role in the development of cardiovascular disease. We examined whether plasma TNF-
is related to established cardiovascular risk indicators, plasma levels of soluble cellular adhesion molecules and carotid artery intimamedia thickness determined by ultrasound examination in a population-based cohort of 96 healthy 50-year-old men.
Methods and Results TNF-
and cellular adhesion molecules were measured with enzyme-linked immunosorbent assays. Plasma TNF-
concentration was associated with systolic and diastolic blood pressure, degrees of alimentary lipaemia, plasma very low density lipoprotein triglyceride, low density lipoprotein (LDL) cholesterol concentrations and peak LDL particle size. Two indices of insulin resistance as well as all soluble cellular adhesion molecules correlated positively with TNF-
. The plasma TNF-
concentration was associated with common carotid intimamedia thickness in univariate analysis. In contrast, soluble E-selectin and postprandial triglycerides, but not TNF-
, were independent determinants of common carotid intimamedia thickness.
Conclusion The plasma TNF-
concentration is associated with degrees of early atherosclerosis and correlates with metabolic and cellular perturbations that are considered important for the vascular process.
Key Words: Atherosclerosis, common carotid intimamedia thickness, tumour necrosis factor-
, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin
f1 Correspondence: Tiina Skoog MSc, King Gustaf V Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden.
References
- Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411452[CrossRef][ISI][Medline]
- Beutler B. TNF, immunity and inflammatory disease: lessons of the past decade. J Investig Med. 1995;43:227235[ISI][Medline]
- Beutler B, Cerami A. The biology of cachectin/TNFa primary mediator of the host response. Annu Rev Immunol. 1989;7:625655[ISI][Medline]
- Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:8791
[Abstract/Free Full Text] - Hotamisligil GS, Spiegelman BM. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes. 1994;43:12711278[Abstract]
- Jovinge S, Hamsten A, Tornvall P. Evidence for a role of tumor necrosis factor alpha in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease. Metabolism. 1998;47:113118[CrossRef][ISI][Medline]
- Libby P, Ridker PM. Novel inflammatory markers of coronary risk: theory versus practice. Circulation. 1999;100:11481150
[Free Full Text] - Cybulsky MI, Gimbrone MA Jr. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991;251:788791
[Abstract/Free Full Text] - Hwang SJ, Ballantyne CM, Sharrett AR. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study. Circulation. 1997;96:42194225
[Abstract/Free Full Text] - Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer MJ, Allen J. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet. 1998;351:8892[CrossRef][ISI][Medline]
- Poston RN, Haskard DO, Coucher JR, Gall NP, Johnson-Tidey RR. Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol. 1992;140:665673[Abstract]
- Printseva O, Peclo MM, Gown AM. Various cell types in human atherosclerotic lesions express ICAM-1. Further immunocytochemical and immunochemical studies employing monoclonal antibody 10F3. Am J Pathol. 1992;140:889896[Abstract]
- van der Wal AC, Das PK, Tigges AJ, Becker AE. Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. Am J Pathol. 1992;141:14271433[Abstract]
- O'Brien KD, McDonald TO, Chait A, Allen MD, Alpers CE. Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. Circulation. 1996;93:672682
[Abstract/Free Full Text] - De Caterina R, Basta G, Lazzerini G. Soluble vascular cell adhesion molecule-1 as a biohumoral correlate of atherosclerosis. Arterioscler Thromb Vasc Biol. 1997;17:26462654
[Abstract/Free Full Text] - Rohde LE, Lee RT, Rivero J. Circulating cell adhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis. Arterioscler Thromb Vasc Biol. 1998;18:17651770
[Abstract/Free Full Text] - Otsuki M, Hashimoto K, Morimoto Y, Kishimoto T, Kasayama S. Circulating vascular cell adhesion molecule-1 (VCAM-1) in atherosclerotic NIDDM patients. Diabetes. 1997;46:20962101[Abstract]
- Peter K, Nawroth P, Conradt C. Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin. Arterioscler Thromb Vasc Biol. 1997;17:505512
[Abstract/Free Full Text] - Boquist S, Ruotolo G, Tang R. Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intimamedia thickness in healthy, middle-aged men. Circulation. 1999;100:723728
[Abstract/Free Full Text] - Carlson K. Lipoprotein fractionation. J Clin Pathol. 1973;5:3237
- Karpe F, Steiner G, Olivecrona T, Carlson LA, Hamsten A. Metabolism of triglyceride-rich lipoproteins during alimentary lipemia. J Clin Invest. 1993;91:748758[ISI][Medline]
- Karpe F, Hamsten A. Determination of apolipoproteins B-48 and B-100 in triglyceride-rich lipoproteins by analytical SDS-PAGE. J Lipid Res. 1994;35:13111317[Abstract]
- Skoglund-Andersson C, Tang R, Bond MG, de Faire U, Hamsten A, Karpe F. LDL particle size distribution is associated with carotid intimamedia thickness in healthy 50-year-old men. Arterioscler Thromb Vasc Biol. 1999;19:24222430
[Abstract/Free Full Text] - Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412419[CrossRef][ISI][Medline]
- Mercuri M, Tang R, Phillips RM, Bond MG. Ultrasound protocol and quality control procedures in the European Lacidipine Study on Atherosclerosis (ELSA). Blood Press Suppl. 1996;4:2023[Medline]
- Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation. 2000;101:21492153
[Abstract/Free Full Text] - Skoog T, van 't Hooft FM, Kallin B. A common functional polymorphism (C
A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum Mol Genet. 1999;8:14431449[Abstract/Free Full Text] - Ross R. Atherosclerosisan inflammatory disease. N Engl J Med. 1999;340:115126
[Free Full Text] - Meager A. Cytokine regulation of cellular adhesion molecule expression in inflammation. Cytokine Growth Factor Rev. 1999;10:2739[CrossRef][ISI][Medline]
- Feingold KR, Grunfeld C. Tumour necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo. J Clin Invest. 1987;80:184190[ISI][Medline]
- Raina N, Matsui J, Cunnane SC, Jeejeebhoy KN. Effect of tumor necrosis factor-alpha on triglyceride and phospholipid content and fatty acid composition of liver and carcass in rats. Lipids. 1995;30:713718[ISI][Medline]
- Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:24092415[ISI][Medline]
- Kanety H, Feinstein R, Papa MZ, Hemi R, Karasik A. Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. J Biol Chem. 1995;270:2378023784
[Abstract/Free Full Text] - Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665668[Abstract]
- Stephens JM, Pekala PH. Transcriptional repression of the GLUT4 and C/EBP genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. J Biol Chem. 1991;266:2183921845
[Abstract/Free Full Text] - Kahaleh MB, Fan PS. Effect of cytokines on the production of endothelin by endothelial cells. Clin Exp Rheumatol. 1997;15:163167[ISI][Medline]
- Brasier AR, Li J, Wimbish KA. Tumor necrosis factor activates angiotensinogen gene expression by the Rel A transactivator. Hypertension. 1996;27:10091017
[Abstract/Free Full Text]
This article has been cited by other articles:
![]() |
S. Xanthoulea, M. J.J. Gijbels, I. van der Made, H. Mujcic, M. Thelen, M. N. Vergouwe, M. H.C. Ambagts, M. H. Hofker, and M. P.J. de Winther p55 Tumour necrosis factor receptor in bone marrow-derived cells promotes atherosclerosis development in low-density lipoprotein receptor knock-out mice Cardiovasc Res, August 5, 2008; (2008) cvn193v2. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Qin, R. A. Anderson, and K. Adeli Tumor necrosis factor-{alpha} directly stimulates the overproduction of hepatic apolipoprotein B100-containing VLDL via impairment of hepatic insulin signaling Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1120 - G1129. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Marfella, C. Di Filippo, M. Portoghese, F. Ferraraccio, B. Crescenzi, M. Siniscalchi, M. Barbieri, C. Bologna, M. R. Rizzo, F. Rossi, et al. Proteasome Activity as a Target of Hormone Replacement Therapy-Dependent Plaque Stabilization in Postmenopausal Women Hypertension, April 1, 2008; 51(4): 1135 - 1141. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Erridge, T. Attina, C. M Spickett, and D. J Webb A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1286 - 1292. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Popa, F. H J van den Hoogen, T. R D J Radstake, M. G Netea, A. E Eijsbouts, M. d. Heijer, J. W M van der Meer, P. L C M van Riel, A. F H Stalenhoef, and P. Barrera Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritis Ann Rheum Dis, November 1, 2007; 66(11): 1503 - 1507. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Rajesh, P. Mukhopadhyay, S. Batkai, G. Hasko, L. Liaudet, J. W. Huffman, A. Csiszar, Z. Ungvari, K. Mackie, S. Chatterjee, et al. CB2-receptor stimulation attenuates TNF-{alpha}-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2210 - H2218. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Del Porto, B. Lagana, S. Lai, I. Nofroni, F. Tinti, M. Vitale, E. Podesta, A. P. Mitterhofer, and R. D'Amelio Response to anti-tumour necrosis factor alpha blockade is associated with reduction of carotid intima-media thickness in patients with active rheumatoid arthritis Rheumatology, July 1, 2007; 46(7): 1111 - 1115. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Popa, M. G. Netea, P. L. C. M. van Riel, J. W. M. van der Meer, and A. F. H. Stalenhoef The role of TNF-{alpha} in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk J. Lipid Res., April 1, 2007; 48(4): 751 - 762. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Zhao, T. D Etherton, K. R Martin, P. J Gillies, S. G West, and P. M Kris-Etherton Dietary {alpha}-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects Am. J. Clinical Nutrition, February 1, 2007; 85(2): 385 - 391. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. A. G. REIS, M. G. REIS, R. DE CASSIA R. SILVA, T. M. A. CARMO, A. M. O. ASSIS, M. L. BARRETO, I. M. PARRAGA, M. L. P. SANTANA, and R. E. BLANTON BIOCHEMICAL AND IMMUNOLOGIC PREDICTORS OF EFFICACY OF TREATMENT OR REINFECTION RISK FOR SCHISTOSOMA MANSONI Am J Trop Med Hyg, November 1, 2006; 75(5): 904 - 909. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Ryan, C. T. Taylor, and W. T. McNicholas Predictors of Elevated Nuclear Factor-{kappa}B-dependent Genes in Obstructive Sleep Apnea Syndrome Am. J. Respir. Crit. Care Med., October 1, 2006; 174(7): 824 - 830. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Nasir, E. Guallar, A. Navas-Acien, M. H. Criqui, and J. A.C. Lima Relationship of Monocyte Count and Peripheral Arterial Disease: Results From the National Health and Nutrition Examination Survey 1999-2002 Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1966 - 1971. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Y Stokes and D. N. Granger The microcirculation: a motor for the systemic inflammatory response and large vessel disease induced by hypercholesterolaemia? J. Physiol., February 1, 2005; 562(3): 647 - 653. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Minoguchi, T. Tazaki, T. Yokoe, H. Minoguchi, Y. Watanabe, M. Yamamoto, and M. Adachi Elevated Production of Tumor Necrosis Factor-{alpha} by Monocytes in Patients With Obstructive Sleep Apnea Syndrome Chest, November 1, 2004; 126(5): 1473 - 1479. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.J. Joshipura, H.C. Wand, A.T. Merchant, and E.B. Rimm Periodontal Disease and Biomarkers Related to Cardiovascular Disease J. Dent. Res., February 1, 2004; 83(2): 151 - 155. [Abstract] [Full Text] [PDF] |
||||
![]() |
L S Rallidis, M G Zolindaki, P C Pentzeridis, K P Poulopoulos, A H Velissaridou, and T S Apostolou Raised concentrations of macrophage colony stimulating factor in severe unstable angina beyond the acute phase are strongly predictive of long term outcome Heart, January 1, 2004; 90(1): 25 - 29. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. D. Sesso, J. E. Buring, N. Rifai, G. J. Blake, J. M. Gaziano, and P. M. Ridker C-Reactive Protein and the Risk of Developing Hypertension JAMA, December 10, 2003; 290(22): 2945 - 2951. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Cesari, B. W.J.H. Penninx, A. B. Newman, S. B. Kritchevsky, B. J. Nicklas, K. Sutton-Tyrrell, S. M. Rubin, J. Ding, E. M. Simonsick, T. B. Harris, et al. Inflammatory Markers and Onset of Cardiovascular Events: Results From the Health ABC Study Circulation, November 11, 2003; 108(19): 2317 - 2322. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. P. Miller, Y.-F. Chen, D. Xing, W. Feng, and S. Oparil Hormone Replacement Therapy and Inflammation: Interactions in Cardiovascular Disease Hypertension, October 1, 2003; 42(4): 657 - 663. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Haider, I. Lee, J. Grabarek, Z. Darzynkiewicz, and N. R. Ferreri Dual Functionality of Cyclooxygenase-2 as a Regulator of Tumor Necrosis Factor-Mediated G1 Shortening and Nitric Oxide-Mediated Inhibition of Vascular Smooth Muscle Cell Proliferation Circulation, August 26, 2003; 108(8): 1015 - 1021. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. W. Saeed, T. Peng, and C. N. Metz Ascorbic Acid Blocks the Growth Inhibitory Effect of Tumor Necrosis Factor-{alpha} on Endothelial Cells Experimental Biology and Medicine, July 1, 2003; 228(7): 855 - 865. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Fernandez-Real and W. Ricart Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome Endocr. Rev., June 1, 2003; 24(3): 278 - 301. [Abstract] [Full Text] [PDF] |
||||
![]() |
E Svenungsson, G-Z Fei, K Jensen-Urstad, U de Faire, A Hamsten, and J Frostegard TNF-{alpha}: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease Lupus, June 1, 2003; 12(6): 454 - 461. [Abstract] [PDF] |
||||
![]() |
H. Bruunsgaard, H. E. Poulsen, B. K. Pedersen, K. Nyyssonen, J. Kaikkonen, and J. T. Salonen Long-Term Combined Supplementations with {alpha}-Tocopherol and Vitamin C Have No Detectable Anti-Inflammatory Effects in Healthy Men J. Nutr., April 1, 2003; 133(4): 1170 - 1173. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. B. Twickler, G. M. Dallinga-Thie, F. L. J. Visseren, W. R. de Vries, D. W. Erkelens, and H. P. F. Koppeschaar Induction of Postprandial Inflammatory Response in Adult Onset Growth Hormone Deficiency Is Related to Plasma Remnant-Like Particle-Cholesterol Concentration J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1228 - 1233. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Hurlimann, A. Forster, G. Noll, F. Enseleit, R. Chenevard, O. Distler, M. Bechir, L. E. Spieker, M. Neidhart, B. A. Michel, et al. Anti-Tumor Necrosis Factor-{alpha} Treatment Improves Endothelial Function in Patients With Rheumatoid Arthritis Circulation, October 22, 2002; 106(17): 2184 - 2187. [Abstract] [Full Text] [PDF] |
||||
![]() |
G.J. Blake and P.M. Ridker Tumour necrosis factor-{alpha}, inflammatory biomarkers, and atherogenesis Eur. Heart J., March 1, 2002; 23(5): 345 - 347. [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||























