Zusammenfassung
ZIELSETZUNG: Das metabolische Syndrom (MetS) ist eine Ansammlung bestimmter Risikofaktoren, die eine starke Assoziation mit Koronarer Herzkrankheit (KHK) aufweisen. Erhöhte Serumspiegel von Plasminogen Aktivator Inhibitor (PAI-1), Interleukin-6 (IL-6) und IL-18 wurden mit KHK in Verbindung gebracht. Rezente Arbeiten haben gezeigt, dass besonders IL-18 in Patienten mit MetS ein guter Prädiktor füer KHK ist. METHODEN: Wir haben die Expression von PAI-1, IL-6 und IL-18 in subkutanem Fettgewebe in Patienten mit (n = 22) und ohne (n = 36) MetS mittels Real-Time-PCR untersucht. Darüber hinaus haben wir die Expression von IL-18 in Makrophagen in einem in vitro Modell für Hyperglykämie analysiert. Nach Isolation von Monozyten und Differenzierung zu Makrophagen wurde die Expression von IL-18 mittels Real-Time-PCR analysiert. ERGEBNISSE: Die Expression von IL-18 im subkutanen Fettgewebe von Patienten mit MetS ist erhöht (p < 0.05). Eine multivariate Analyse zeigte, dass Nüchtern-Blutzucker die einzige der MetS Komponenten ist, die unabhängig mit IL-18 Expression im Fettgewebe assoziiert ist (p < 0.05). Die Makrophagen im hyperglykämen Milieu hatten eine deutlich höhere IL-18 Expression (p < 0.01), als jene im normoglykämen Milieu. SCHLUSSFOLGERUNG: Unsere Daten sprechen sprechen füer eine spezielle inflammatorische Situation im subkutanen Fettgewebe von Patienten mit MetS, die möglicherweise von Hyperglykämie beeinflusst wird. Makrophagen im subkutanen Fettgewebe könnten zumindest teilweise der zelluläre Ursprung für die erhöhte IL-18 Produktion sein. Zusammen mit rezenten Arbeiten, die IL-18 als Prädiktor füer KHK identifiziert haben, stärken unsere Daten die Möglichkeit einer wichtigen Rolle füer IL-18 als Verbindungsglied zwischen MetS und Atherosklerose.
Summary
BACKGROUND: The metabolic syndrome (MetS) is a cluster of risk factors that are highly associated with increased risk for cardiovascular disease (CVD). Increased serum levels of plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6) and IL-18 have been reported to be associated with CVD. Recently, IL-18 has been shown to be predictive for cardiovascular events in subjects with MetS. We have investigated the expression of PAI-1, IL-6 and IL-18 in subcutaneous adipose tissue (AT) of subjects with (n = 22) and without (n = 36) MetS. Furthermore, we have analysed the expression of IL-18 in monocyte-derived macrophages (MDMs) in an in vitro model of hyperglycaemia. METHODS: We studied the expression of PAI-1, IL-6 and IL-18 in biopsies of subcutaneous adipose tissue using Real-time PCR. After isolation and cultivation of MDMs, expression of IL-18 was determined by Real-time PCR. RESULTS: Expression of IL-18 was increased in subcutaneous AT of subjects with MetS (p < 0.05). Multivariate analysis revealed fasting plasma glucose to be the only MetS component being independently associated with expression of IL-18 in AT (p < 0.05). Exposure to hyperglycaemia, increased in expression of IL-18 in MDMs (p < 0.01). CONCLUSION: Our findings suggest that subjects with MetS have a particular inflammatory pattern in AT, possibly driven by fasting glucose. MDMs might - at least in part - be the cellular source of this increased expression. Together with recent reports, showing IL-18 to be predictive for cardiovascular events, our findings could provide the basis for further research of the role of IL-18 as a link and possible target in the association between MetS and atherosclerosis.
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Weiss, T., Arnesen, H., Trøseid, M. et al. Adipose tissue expression of interleukin-18 mRNA is elevated in subjects with metabolic syndrome and independently associated with fasting glucose. Wien Klin Wochenschr 123, 650–654 (2011). https://doi.org/10.1007/s00508-011-0028-6
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DOI: https://doi.org/10.1007/s00508-011-0028-6