From the Section of Clinical Immunology and Infectious Diseases (P.A.,
F.M., I.N., S.S.F.) and Research Institute for Internal Medicine (P.A., F.M.,
I.N., S.S.F.), Medical Department A, and the Section of Cardiology (T.U.,
A.K.A., H.A., J.K., S.S., L.G.), Medical Department B, University of Oslo,
Rikshospitalet, Oslo, Norway.
Correspondence to Pål Aukrust, MD, PhD, Section of Clinical Immunology and Infectious Diseases, Medical Department A, Rikshospitalet, N-0027 Oslo, Norway. E-mail pal.aukrust{at}klinmed.uio.no
Background—Immunologic and
inflammatory responses appear to play a pathogenic role in the
development of congestive heart failure (CHF). Activation and migration
of leukocytes to areas of inflammation are important factors in these
immunologic responses. Because the C-C chemokines are potent
chemoattractants of monocytes and lymphocytes and can modulate other
functions of these cells (eg, generation of reactive oxygen species),
we measured circulating levels of three C-C chemokines in CHF.
Methods and Results—Levels of macrophage chemoattractant
protein-1 (MCP-1), macrophage inflammatory protein-1
Conclusions—This first demonstration of increased circulating
levels of C-C chemokines in CHF with particularly high levels in
patients with severe disease may represent previously
unrecognized pathogenic factors in CHF.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Elevated Circulating Levels of C-C Chemokines in Patients With Congestive Heart Failure
(MIP-1), and RANTES (regulated on
activation normally T-cell
expressed and secreted) were measured by
enzyme immunoassays in 44 patients with CHF and 21 healthy control
subjects. CHF patients had significantly elevated levels of all
chemokines with the highest levels in New York Heart Association class
IV, and MCP-1 and MIP-1 levels were significantly inversely
correlated with left ventricular ejection fraction.
Elevated C-C chemokine levels were found independent of the cause of
the heart failure, but MCP-1 levels were particularly raised in
patients with coronary artery disease. Studies on cells
isolated from peripheral blood suggested that
platelets, CD3+ lymphocytes, and in particular, monocytes, might
contribute to the elevated C-C chemokine levels in CHF. The increased
MCP-1 levels in CHF were correlated with increased monocyte activity
reflected in an enhancing effect of serum from CHF patients on
O2- generation in monocytes, which was
inhibited by neutralizing antibodies against MCP-1.
Key Words: heart failure • coronary disease • chemokines • free radicals • monocytes
This article has been cited by other articles:
 |
|
 |
|
  P. Misra, D. Lebeche, H. Ly, M. Schwarzkopf, G. Diaz, R. J. Hajjar, A. D. Schecter, and J. V. Frangioni Quantitation of CXCR4 Expression in Myocardial Infarction Using 99mTc-Labeled SDF-1{alpha} J. Nucl. Med., June 1, 2008; 49(6): 963 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Kavsak, D. T. Ko, A. M. Newman, G. E. Palomaki, V. Lustig, A. R. MacRae, and A. S. Jaffe Risk Stratification for Heart Failure and Death in an Acute Coronary Syndrome Population Using Inflammatory Cytokines and N-Terminal Pro-Brain Natriuretic Peptide Clin. Chem., December 1, 2007; 53(12): 2112 - 2118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Khaleduzzaman, J. Francis, M. E. Corbin, E. McIlwain, M. Boudreaux, M. Du, T. W. Morgan, and K. E. Peterson Infection of Cardiomyocytes and Induction of Left Ventricle Dysfunction by Neurovirulent Polytropic Murine Retrovirus J. Virol., November 15, 2007; 81(22): 12307 - 12315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Chung and G. Y.H. Lip Platelets and heart failure Eur. Heart J., November 2, 2006; 27(22): 2623 - 2631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. van Kimmenade, J. L. Januzzi Jr, P. T. Ellinor, U. C. Sharma, J. A. Bakker, A. F. Low, A. Martinez, H. J. Crijns, C. A. MacRae, P. P. Menheere, et al. Utility of Amino-Terminal Pro-Brain Natriuretic Peptide, Galectin-3, and Apelin for the Evaluation of Patients With Acute Heart Failure J. Am. Coll. Cardiol., September 19, 2006; 48(6): 1217 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sun, R. A. Ahokas, S. K. Bhattacharya, I. C. Gerling, L. D. Carbone, and K. T. Weber Oxidative stress in aldosteronism Cardiovasc Res, July 15, 2006; 71(2): 300 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bidzhekov, A. Zernecke, and C. Weber MCP-1 Induces a Novel Transcription Factor With Proapoptotic Activity Circ. Res., May 12, 2006; 98(9): 1107 - 1109. [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Holven, J. K. Damas, A. Yndestad, T. Waehre, T. Ueland, B. Halvorsen, L. Heggelund, W. J. Sandberg, A. G. Semb, S. S. Froland, et al. Chemokines in Children With Heterozygous Familiar Hypercholesterolemia: Selective Upregulation of RANTES Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 200 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Enomoto, M Yoshiyama, T Omura, R Matsumoto, T Kusuyama, S Kim, Y Izumi, K Akioka, H Iwao, K Takeuchi, et al. Effects of eplerenone on transcriptional factors and mRNA expression related to cardiac remodelling after myocardial infarction Heart, December 1, 2005; 91(12): 1595 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chakrabarti, S. Varghese, O. Vitseva, K. Tanriverdi, and J. E. Freedman CD40 Ligand Influences Platelet Release of Reactive Oxygen Intermediates Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2428 - 2434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Cullen, S. Sayeed, Y. Jin, N. G. Theodorakis, J. V. Sitzmann, P. A. Cahill, and E. M. Redmond Ethanol inhibits monocyte chemotactic protein-1 expression in interleukin-1{beta}-activated human endothelial cells Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1669 - H1675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Schiotz Thorud, A. Stranda, J.-A. Birkeland, P. K. Lunde, I. Sjaastad, S. O. Kolset, O. M. Sejersted, and P. O. Iversen Enhanced matrix metalloproteinase activity in skeletal muscles of rats with congestive heart failure Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R389 - R394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Athanassopoulos, L. M.B. Vaessen, A. P.W.M. Maat, A. H.M.M. Balk, W. Weimar, and A. J.J.C. Bogers Peripheral blood dendritic cells in human end-stage heart failure and the early post-transplant period: evidence for systemic Th1 immune responses Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 619 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Ahokas, K. J. Warrington, I. C. Gerling, Y. Sun, L. A. Wodi, P. A. Herring, L. Lu, S. K. Bhattacharya, A. E. Postlethwaite, and K. T. Weber Aldosteronism and Peripheral Blood Mononuclear Cell Activation: A Neuroendocrine-Immune Interface Circ. Res., November 14, 2003; 93 (10): e124 - e135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hayashidani, H. Tsutsui, T. Shiomi, M. Ikeuchi, H. Matsusaka, N. Suematsu, J. Wen, K. Egashira, and A. Takeshita Anti-Monocyte Chemoattractant Protein-1 Gene Therapy Attenuates Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction Circulation, October 28, 2003; 108(17): 2134 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yndestad, A. M Holm, F. Muller, S. Simonsen, S. S Froland, L. Gullestad, and P. Aukrust Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure Cardiovasc Res, October 15, 2003; 60(1): 141 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Murphy, K. R. Bruckdorfer, D. C. Grimsditch, P. Overend, M. Vidgeon-Hart, P. H.E. Groot, G. M. Benson, and A. Graham Temporal Relationships Between Circulating Levels of CC and CXC Chemokines and Developing Atherosclerosis in Apolipoprotein E*3 Leiden Mice Arterioscler. Thromb. Vasc. Biol., September 1, 2003; 23(9): 1615 - 1620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-Y. Li, C.-S. Tsai, S.-H. Chueh, P.-C. Hsu, J.-Y. Wang, C.-S. Wong, and S.-T. Ho Dobutamine Inhibits Monocyte Chemoattractant Protein-1 Production and Chemotaxis in Human Monocytes Anesth. Analg., July 1, 2003; 97(1): 205 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. de Lemos, D. A. Morrow, M. S. Sabatine, S. A. Murphy, C. M. Gibson, E. M. Antman, C. H. McCabe, C. P. Cannon, and E. Braunwald Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndromes Circulation, February 11, 2003; 107(5): 690 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-Y. Li, T.-C. Chou, C.-H. Lee, C.-S. Tsai, S.-H. Loh, and C.-S. Wong Adrenaline Inhibits Lipopolysaccharide-Induced Macrophage Inflammatory Protein-1{alpha} in Human Monocytes: The Role of {beta}-Adrenergic Receptors Anesth. Analg., February 1, 2003; 96(2): 518 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H.M. Lopes, S. S. Vasudevan, D. Gregg, B. Selvakumar, P. J. Pagano, H. Kovacic, and P. J. Goldschmidt-Clermont Rac-Dependent Monocyte Chemoattractant Protein-1 Production Is Induced by Nutrient Deprivation Circ. Res., November 1, 2002; 91(9): 798 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nakamura, K. Egashira, Y. Machida, S. Hayashidani, M. Takeya, H. Utsumi, H. Tsutsui, and A. Takeshita Probucol Attenuates Left Ventricular Dysfunction and Remodeling in Tachycardia-Induced Heart Failure: Roles of Oxidative Stress and Inflammation Circulation, July 16, 2002; 106(3): 362 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Holven, P. Aukrust, T. Holm, L. Ose, and M. S. Nenseter Folic Acid Treatment Reduces Chemokine Release From Peripheral Blood Mononuclear Cells in Hyperhomocysteinemic Subjects Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 699 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Frangogiannis, S. Shimoni, S. M. Chang, G. Ren, K. Shan, C. Aggeli, M. J. Reardon, G. V. Letsou, R. Espada, M. Ramchandani, et al. Evidence for an Active Inflammatory Process in the Hibernating Human Myocardium Am. J. Pathol., April 1, 2002; 160(4): 1425 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.L. Clark, M. Loebe, E.V. Potapov, K. Egerer, C. Knosalla, R. Hetzer, and S.D. Anker Ventricular assist device in severe heart failure. Effects on cytokines, complement and body weight Eur. Heart J., December 2, 2001; 22(24): 2275 - 2283. [Abstract] [PDF]
|
|
|
|
 |
|
 H. KIMURA, O. OKADA, N. TANABE, Y. TANAKA, M. TERAI, Y. TAKIGUCHI, M. MASUDA, N. NAKAJIMA, K. HIROSHIMA, H. INADERA, et al. Plasma Monocyte Chemoattractant Protein-1 and Pulmonary Vascular Resistance in Chronic Thromboembolic Pulmonary Hypertension Am. J. Respir. Crit. Care Med., July 15, 2001; 164(2): 319 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Damas, L. Gullestad, H. Aass, S. Simonsen, J. G. Fjeld, L. Wikeby, T. Ueland, H. G. Eiken, S. S. Froland, and P.a. Aukrust Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure--modulatory effect of intravenous immunoglobulin J. Am. Coll. Cardiol., July 1, 2001; 38(1): 187 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Adamopoulos, J Parissis, C Kroupis, M Georgiadis, D Karatzas, G Karavolias, K Koniavitou, A.J.S Coats, and D.T. Kremastinos Physical training reduces peripheral markers of inflammation in patients with chronic heart failure Eur. Heart J., May 1, 2001; 22(9): 791 - 797. [Abstract] [PDF]
|
|
|
|
|
|
A. M. Schmidt and D. M. Stern Chemokines on the Rise : MCP-1 and Restenosis Arterioscler. Thromb. Vasc. Biol., March 1, 2001; 21(3): 297 - 299. [Full Text] [PDF]
|
|
|
|
|
|
F. Cipollone, M. Marini, M. Fazia, B. Pini, A. Iezzi, M. Reale, L. Paloscia, G. Materazzo, E. D'Annunzio, P. Conti, et al. Elevated Circulating Levels of Monocyte Chemoattractant Protein-1 in Patients With Restenosis After Coronary Angioplasty Arterioscler. Thromb. Vasc. Biol., March 1, 2001; 21(3): 327 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.a. Aukrust, R. K. Berge, T. Ueland, E. Aaser, J. K. Damas, L. Wikeby, A. Brunsvig, F. Muller, K. Forfang, S. S. Froland, et al. Interaction between chemokines and oxidative stress: possible pathogenic role in acute coronary syndromes J. Am. Coll. Cardiol., February 1, 2001; 37(2): 485 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Arimura, K. Egashira, R. Nakamura, T. Ide, H. Tsutsui, H. Shimokawa, and A. Takeshita Increased inactivation of nitric oxide is involved in coronary endothelial dysfunction in heart failure Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H68 - H75. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Clemetson, J. M. Clemetson, A. E. I. Proudfoot, C. A. Power, M. Baggiolini, and T. N. C. Wells Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets Blood, December 15, 2000; 96(13): 4046 - 4054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rossig, J. Haendeler, Z. Mallat, B. Hugel, J.-M. Freyssinet, A. Tedgui, S. Dimmeler, and A. M. Zeiher Congestive heart failure induces endothelial cell apoptosis: protective role of carvedilol J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2081 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Behr, X. Wang, N. Aiyar, R. W. Coatney, X. Li, P. Koster, C. E. Angermann, E. Ohlstein, G. Z. Feuerstein, and J. Winaver Monocyte Chemoattractant Protein-1 is Upregulated in Rats With Volume-Overload Congestive Heart Failure Circulation, September 12, 2000; 102(11): 1315 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Damas, H. G. Eiken, E. Oie, V. Bjerkeli, A. Yndestad, T. Ueland, T. Tonnessen, O. R. Geiran, H. Aass, S. Simonsen, et al. Myocardial expression of CC- and CXC-chemokines and their receptors in human end-stage heart failure Cardiovasc Res, September 1, 2000; 47(4): 778 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Berry and A.L Clark Catabolism in chronic heart failure Eur. Heart J., April 1, 2000; 21(7): 521 - 532. [PDF]
|
|
|
|
 |
|
 W. B Strawn, R. H Dean, and C. M Ferrario Novel mechanisms linking angiotensin II and early atherogenesis Journal of Renin-Angiotensin-Aldosterone System, March 1, 2000; 1(1): 11 - 17. [PDF]
|
|
|
|
 |
|
 T. Stefanec Endothelial Apoptosis: Could It Have a Role in the Pathogenesis and Treatment of Disease? Chest, March 1, 2000; 117(3): 841 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sasayama, M. Okada, and A. Matsumori Chemokines and cardiovascular diseases Cardiovasc Res, January 14, 2000; 45(2): 267 - 269. [Full Text] [PDF]
|
|
|
|
|
|
J. K. Damas, L. Gullestad, T. Ueland, N. O. Solum, S. Simonsen, S. S Froland, and P. Aukrust CXC-chemokines, a new group of cytokines in congestive heart failure -- possible role of platelets and monocytes Cardiovasc Res, January 14, 2000; 45(2): 428 - 436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gullestad, P.a. Aukrust, T. Ueland, T. Espevik, G. Yee, R. Vagelos, S. S. Froland, and M. Fowler Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2061 - 2067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Aukrust, F. Muller, T. Ueland, T. Berget, E. Aaser, A. Brunsvig, N. O. Solum, K. Forfang, S. S. Froland, and L. Gullestad Enhanced Levels of Soluble and Membrane-Bound CD40 Ligand in Patients With Unstable Angina : Possible Reflection of T Lymphocyte and Platelet Involvement in the Pathogenesis of Acute Coronary Syndromes Circulation, August 10, 1999; 100(6): 614 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sasayama, A. Matsumori, and Y. Kihara New insights into the pathophysiological role for cytokines in heart failure Cardiovasc Res, June 1, 1999; 42(3): 557 - 564. [Full Text] [PDF]
|
|
|
|
|
|
K. B. Holven, P. Aukrust, T. Holm, L. Ose, and M. S. Nenseter Folic Acid Treatment Reduces Chemokine Release From Peripheral Blood Mononuclear Cells in Hyperhomocysteinemic Subjects Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 699 - 703. [Abstract] [Full Text] [PDF]
|
|