on October 20, 2005
Published online before print October 20, 2005, doi: 10.1161/01.ATV.0000191633.52585.14
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 12, 2004
Accepted on October 5, 2005
Differential Expression of Chemokines, Risk of Stable Coronary Heart Disease, and Correlation with Established Cardiovascular Risk Markers
Dietrich Rothenbacher ;
From the Department of Epidemiology (D.R.), The German Centre for Research on Ageing, University of Heidelberg; German Diabetes Clinic (S.M.-S., C.H., H.K.), German Diabetes Center at Heinrich Heine University Duesseldorf; and the Department of Internal Medicine II-Cardiology (W.K.), University of Ulm Medical Center, Ulm, Germany.
* To whom correspondence should be addressed. E-mail: wolfgang.koenig{at}medizin.uni-ulm.de.
Objective--We investigated the association of several chemokines with the risk of stable coronary heart disease (CHD) in a large case-control study after adjustment for other established risk factors. Furthermore, we analyzed their correlation with various acute-phase proteins, inflammation-associated cytokines, and an adhesion molecule.
Methods and Results--We included 312 patients aged 40 to 68 years with angiographically confirmed and stable CHD and 472 age- and gender-matched controls in this study. The main outcome measure was the odds ratio (OR) for CHD associated with increased levels of interferon (INF)-inducible protein of 10 kd (IP-10), interleukin (IL)-8, regulated on activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammation protein 1
(MIP-1), or eotaxin determined by rigidly evaluated sandwich ELISAs. Serum levels of IP-10 and IL-8 were higher, and serum levels of RANTES were lower in CHD patients when compared with age- and gender-matched controls. In addition, values in the second and top tertile of IP-10 and IL-8 were associated with an increased OR for CHD when compared with values in the bottom tertile [OR for IP-10 (top tertile) was 2.62 (95% CI, 1.79 to 3.85) in the age- and gender-adjusted model and 1.93 (95% CI, 1.23 to 3.04) in the fully adjusted model, and for IL-8, the OR was 1.77 (95% CI, 1.20 to 2.59) and 1.53 (95% CI, 0.98 to 2.39), respectively]; increased RANTES values were associated with a lower OR for CHD [OR, 0.67 (95% CI, 0.47 to 0.96) and 0.61 (95% CI, 0.40 to 0.94)]. Furthermore, positive correlations of IP-10 and IL-8 with several acute-phase proteins or inflammation-associated cytokines were evident, and positive correlations for IP-10 plasma viscosity and intercellular adhesion molecule 1 were also present.
Conclusions--The current study suggests that there may be no universal upregulation of chemokines in CHD-associated inflammation but different upregulation of IP-10 and IL-8 versus downregulation of RANTES; there was no clear disease association for MCP-1, MIP-1, or eotaxin.
Key words: chemokines • coronary heart disease • inflammation • case-control study
This article has been cited by other articles:
 |
|
 |
|
  P. Aukrust, B. Halvorsen, A. Yndestad, T. Ueland, E. Oie, K. Otterdal, L. Gullestad, and J. K. Damas Chemokines and Cardiovascular Risk Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1909 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Wong, M. Freiberg, R. Tracy, and L. Kuller Epidemiology of Cytokines: The Women On the Move through Activity and Nutrition (WOMAN) Study Am. J. Epidemiol., August 15, 2008; 168(4): 443 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Koizumi, T. Kurita-Ochiai, S. Oguchi, and M. Yamamoto Nasal Immunization with Porphyromonas gingivalis Outer Membrane Protein Decreases P. gingivalis-Induced Atherosclerosis and Inflammation in Spontaneously Hyperlipidemic Mice Infect. Immun., July 1, 2008; 76(7): 2958 - 2965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ardigo, T. L. Assimes, S. P. Fortmann, A. S. Go, M. Hlatky, E. Hytopoulos, C. Iribarren, P. S. Tsao, R. Tabibiazar, T. Quertermous, et al. Circulating chemokines accurately identify individuals with clinically significant atherosclerotic heart disease Physiol Genomics, November 14, 2007; 31(3): 402 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.O. Kraaijeveld, S.C.A. de Jager, W.J. de Jager, B.J. Prakken, S.R. McColl, I. Haspels, H. Putter, T.J.C. van Berkel, L. Nagelkerken, J.W. Jukema, et al. CC Chemokine Ligand-5 (CCL5/RANTES) and CC Chemokine Ligand-18 (CCL18/PARC) Are Specific Markers of Refractory Unstable Angina Pectoris and Are Transiently Raised During Severe Ischemic Symptoms Circulation, October 23, 2007; 116(17): 1931 - 1941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Cavusoglu, C. Eng, V. Chopra, L. T. Clark, D. J. Pinsky, and J. D. Marmur Low Plasma RANTES Levels Are an Independent Predictor of Cardiac Mortality in Patients Referred for Coronary Angiography Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 929 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Skurk, C. Alberti-Huber, C. Herder, and H. Hauner Relationship between Adipocyte Size and Adipokine Expression and Secretion J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1023 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Herder, J. Baumert, B. Thorand, S. Martin, H. Lowel, H. Kolb, and W. Koenig Chemokines and Incident Coronary Heart Disease: Results From the MONICA/KORA Augsburg Case-Cohort Study, 1984-2002 Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 2147 - 2152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Herder, H. Hauner, B. Haastert, K. Rohrig, W. Koenig, H. Kolb, S. Muller-Scholze, B. Thorand, R. Holle, and W. Rathmann Hypoadiponectinemia and Proinflammatory State: Two Sides of the Same Coin?: Results From the Cooperative Health Research in the Region of Augsburg Survey 4 (KORA S4) Diabetes Care, July 1, 2006; 29(7): 1626 - 1631. [Abstract] [Full Text] [PDF]
|
|