CLINICAL STUDY: ACUTE CORONARY SYNDROMES
Interaction between chemokines and oxidative stress: possible pathogenic role in acute coronary syndromes
P.ål Aukrust, MD, PhD*  ,
Rolf K. Berge, PhD ,
Thor Ueland, BS ,
Ellinor Aaser, MD||,
Jan Kristian Damås, MD ||,
Lisbeth Wikeby, RN ||,
Anne Brunsvig, BS||,
Fredrik Müller, MD, PhD* ,
Kolbjørn Forfang, MD, PhD||,
Stig S. Frøland, MD, PhD* and
Lars Gullestad, MD, PhD||
* Section of Clinical Immunology and Infectious Diseases, Rikshospitalet, Oslo, Norway
Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway
Section of Endocrinology, Medical Department, Rikshospitalet, Oslo, Norway
|| Department of Cardiology, Rikshospitalet, Oslo, Norway
Department of Clinical Biology, Division of Clinical Biochemistry, Haukeland Hospital, Bergen, Norway
Manuscript received May 8, 2000;
revised manuscript received August 21, 2000,
accepted October 2, 2000.
Reprint requests and correspondence: Dr. Pål Aukrust, Section of Clinical Immunology and Infectious Diseases, Medical Department, Rikshospitalet, Sognsvannsveien 20, N-0027 Oslo, Norway
pal.aukrust{at}rikshospital.et
OBJECTIVES
We sought to study the relationships between chemokines and oxidative stress in acute coronary syndrome.
BACKGROUND
In view of existing knowledge on the participation of leukocytes and oxidative stress in the pathogenesis of acute coronary syndrome, we hypothesized that chemokines may play a role in recruiting and activating leukocytes in this disorder.
METHODS
The levels of chemokines and oxidative stress were studied in 38 patients with stable and 38 with unstable angina and in 20 controls. In separate in vitro experiments the effect of chemokines on reactive oxygen species in monocytes and the effect of antioxidants on chemokine levels in these cells were also studied.
RESULTS
1) Angina patients had raised serum levels of chemokines in both cross-sectional and longitudinal testing, with particularly high levels of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory peptide (MIP)-1-alpha in unstable disease. 2) T cells, and particularly monocytes, seem to contribute to the raised IL-8, MCP-1 and MIP-1-alpha levels in unstable angina. 3) Concomitantly, and significantly correlated with MCP-1 and IL-8 levels, stable and particularly unstable angina patients had decreased plasma levels of antioxidants and increased lipid peroxidation, suggesting enhanced oxidative stress. 4) Monocyte chemoattractant protein-1 enhanced the generation of O2– in monocytes from unstable angina patients, and the antioxidant glutathione-monoethyl ester suppressed the production of IL-8 and MCP-1 in these cells.
CONCLUSIONS
Our findings suggest an interaction between chemokines and oxidative stress in unstable angina. This interaction may represent a vicious circle involved in the pathogenesis of acute coronary syndromes.
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Abbreviations and Acronyms
| | CAD | = coronary artery disease | | ENA-78 | = epithelial neutrophil-activating peptide-78 | | GRO-alpha | = growth-regulated oncogene alpha | | IL-8 | = interleukin-8 | | LPS | = lipopolysaccharide | | MCP-1 | = monocyte chemoattractant protein 1 | | MIP-1-alpha | = macrophage inflammatory peptide 1-alpha | | O2– | = superoxide anion | | RANTES | = regulated on activation normally T cell expressed and secreted | | ROS | = reactive oxygen species |
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