Interleukin-18 Is a Strong Predictor of Cardiovascular Death in Stable and Unstable Angina

Blankenberg, Stefan; Tiret, Laurence; Bickel, Christoph; Peetz, D.; Cambien, François; Meyer, Jürgen; Rupprecht, Hans J.

doi:10.1161/01.cir.0000020546.30940.92

Cited by 510 publications

(355 citation statements)

References 42 publications

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“…Several studies have reported the relationship between the IL-12-and IL-18-mediated inflammatory responses and the pathophysiology and prognosis of atherosclerotic diseases. [31][32][33] However, in the current study, the IL-12-and/or IL-18-induced IFN-c secretion by CD8 1 CD57 1 T cells was not greater than that by CD8 1 CD57 2 T cells (Figure 3b), while anti-CD3 antibody-induced IFN-c secretion was significantly higher from the CD8 1 CD57 1 T cell population (Figure 3a). Recently, Hoffmann et al 22 reported the immunophenotypic profiles of T-cell subsets in patients with acute MI following primary percutaneous coronary intervention.…”

Section: Discussioncontrasting

confidence: 63%

Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction

Youn

Lee

et al. 2014

Cell Mol Immunol

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Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction (MI). We studied the immunological characteristics and clinical impact of CD8 1 CD57 1 T cells in acute MI patients. The frequency of CD57 1 cells among CD8 1 T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57 1 cells in the CD8 1 T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8 1 CD57 1 T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8 1 CD57 1 T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8 1 CD57 1 T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8 1 T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8 1 T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.

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Section: Discussioncontrasting

confidence: 63%

Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction

Youn

Lee

et al. 2014

Cell Mol Immunol

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“…This is especially so given that the decrease in IL-18 levels also correlates with better periodontal health. Plasma IL-18 has also been shown to predict death in patients with a pre-existing CVD [22] and also death in initially healthy individuals [23]. Animal models support the role of IL-18 in atherogenesis, and this role has been shown to partly involve an IFN-␥ dependent mechanism [24].…”

Section: Discussionmentioning

confidence: 96%

Periodontal treatment influences risk markers for atherosclerosis in patients with severe periodontitis

et al. 2009

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a b s t r a c tThis study investigated the effect of mechanical infection control for periodontitis and periodontal surgery on the prevalence of well-established risk factors for atherosclerosis, and plasma levels of cytokines, antibodies against heat shock proteins and markers of systemic inflammation.Sixty-eight patients between 39 and 73 years of age with severe periodontitis who had been referred to four specialist periodontology clinics in Sweden were investigated. A fasting venous blood sample was taken at baseline and additional samples were collected after 3 and 12 months. A total of 54 patients underwent periodontal treatment.The periodontal treatment was successful, as pathogenic gingival pockets decreased significantly. Plasma glucose, lipids and markers of systemic inflammation were not significantly altered after 3 months. One year after the initial treatment, HDL-C concentrations were significantly increased ( 0.08 mmol/L) whereas LDL-C concentrations decreased ( 0.23 mmol/L). Haptoglobin concentrations were also lower. Interleukin-18 and interferon-␥ levels were also lower after 12 months (60 ng/L (−23%) and 11 ng/L (−97%) respectively). Treatment had no effect on plasma levels of IgA, IgG1, IgG2 antibodies against heat shock proteins.In conclusion, this study indicates that standard treatment for periodontal disease induces systemic changes in several biochemical markers that reflect the risk for atherosclerosis.

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“…10 Expression of IL-18 has been detected in human atherosclerotic plaques and associated with plaque progression and plaque vulnerability. 11,12 Finally, epidemiological studies have shown that plasma levels of IL-18 were predictive of future cardiovascular events both in healthy subjects and coronary patients, 13,14 although these findings were recently debated. 15 We and others have identified several common polymorphisms in the potentially functional regions of the IL18 gene, including the coding sequence, exon/intron junctions, promoter and untranslated regions (UTRs).…”

Section: Introductionmentioning

confidence: 99%

Differential haplotypic expression of the interleukin-18 gene

et al. 2007

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Interleukin 18 (IL-18) is suspected to play an important role in atherosclerosis and plaque vulnerability. We had previously shown that haplotypes combining two IL18 gene polymorphisms in complete linkage disequilibrium, C-105T (rs360717) in 5 0 -untranslated region (UTR) and A þ 183G (rs5744292) in 3 0 -UTR, were related to IL-18 circulating levels and cardiovascular outcome, the C À105 G þ 183 haplotype being associated with lower IL-18 levels and lower cardiovascular risk. This study was aimed at investigating the functional role of the two polymorphisms and their haplotypes on IL18 expression levels. Allelic imbalance experiments conducted in 24 and 20 subjects heterozygous for the C-105T and the A þ 183G polymorphisms did not detect any difference when subjects were considered as a whole (À0.00970.044, P ¼ 0.85 and þ 0.11470.082, P ¼ 0.18, respectively). However, when splitting individuals according to their haplo-genotype, the haplotype C À105 G þ 183 was associated with a lower expression level than C À105 A þ 183 (À0.28770.076, P ¼ 0.005), but did not differ from T À105 A þ 183 (À0.13870.083, P ¼ 0.13). The lower expression associated with C À105 G þ 183 was confirmed by real-time reverse transcription-PCR. Transfection of different haplotypic versions of the 3 0 -UTR did not show any difference in the expression of an upstream reporter gene. A 10-h study of the mRNA degradation kinetics by allelic imbalance with the A þ 183G polymorphism did not show any differential allelic degradation. In conclusion, the haplotype associated with lower IL-18 circulating concentrations and a lower cardiovascular risk was consistently associated with decreased IL18 expression levels, although the exact functional mechanisms remain to be elucidated.

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Interleukin-18 Is a Strong Predictor of Cardiovascular Death in Stable and Unstable Angina

Cited by 510 publications

References 42 publications

Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction

Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction

Periodontal treatment influences risk markers for atherosclerosis in patients with severe periodontitis

Differential haplotypic expression of the interleukin-18 gene

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