Expression des Makrophagen- Migration- Inhibitions- faktor (MIF) bei Patienten mit koronarer Herzerkrankung und seine Assoziation mit der inflammatorischen Reaktion

Nach heutigem Wissensstand sind die Kenntnisse über die klinische Bedeutung des Makrophagen- Migration- Inhibitionsfaktors (MIF) bei kardiovaskulären Erkrankungen gering. Ziel dieser Arbeit war die Frage, inwieweit die Messung von MIF zur Risikostratifizierung für kardiovaskuläre Erkrankungen in Frage kommt und ob eine Assoziation mit etablierten inflammatorischen Markern vorliegt. Es wurden insgesamt 286 Patienten mit einer symptomatischen- koronaren Herzerkrankung und 25 gesunde Probanden untersucht. Mittels eines anti Makrophagen- Migration- Inhibitionsfaktor- ELISA wurde die MIF- Konzentration im EDTA-Plasma bestimmt und die Assoziation mit etablierten Markern (kardiale Risikofaktoren: Cholesterol, HDL, LDL, Hyperlipidämie, Nikotinabusus und Diabetes mellitus; inflammatorische Marker: CRP, IL-6, MCP-1, Rantes, Monozyten- und Leukozytenzahlen; myokardialer Nekrosemarker: Troponin I; residuelle Thrombozytenaggregation unter dualer Plättchenhemmung) untersucht. Dabei konnte aufgezeigt werden, dass eine erhöhte MIF- Konzentration mit der Erhöhung von etablierten inflammatorischen Markern assoziiert ist, ebenso wie mit einer Erhöhung kardialer Nekrosemarker und dem Auftreten akuter Plaquerupturen. Insgesamt weisen Patienten mit akutem Myokardinfarkt die höchsten MIF-Spiegel im Blut auf, gefolgt von Patienten mit stabiler Angina pectoris. Gesunde Probanden zeigten die niedrigsten Werte für MIF. Der Makrophagen- Migration- Inhibitionsfaktor könnte damit als neuer Biomar-ker für die Vorhersage von Plaquerupturen und der Schwere akuter koronarer Ereignisse herangezogen werden. Zudem könnte eine Therapie, basierend auf einer Beeinflussung der MIF- assoziierten Pathomechanismen, eine mögliche Option für die Behandlung kardiovaskulärer Erkrankungen darstellen

Macrophage Migration Inhibitory Factor Is Enhanced in Acute Coronary Syndromes and Is Associated with the Inflammatory Response

Chronic inflammation promotes atherosclerosis in cardiovascular disease and is a major prognostic factor for patients undergoing percutaneous coronary intervention (PCI). Macrophage migration inhibitory factor (MIF) is involved in the progress of atherosclerosis and plaque destabilization and plays a pivotal role in the development of acute coronary syndromes (ACS). Little is known to date about the clinical impact of MIF in patients with symptomatic coronary artery disease (CAD).In a pilot study, 286 patients with symptomatic CAD (n = 119 ACS, n = 167 stable CAD) undergoing PCI were consecutively evaluated. 25 healthy volunteers served as control. Expression of MIF was consecutively measured in patients at the time of PCI. Baseline levels of interleukin 6 (IL-6), “regulated upon activation, normal T-cell expressed, and secreted” (RANTES) and monocyte chemoattractant protein-1 (MCP-1) were measured by Bio-Plex Cytokine assay. C-reactive protein (CRP) was determined by Immunoassay. Patients with ACS showed higher plasma levels of MIF compared to patients with stable CAD and control subjects (median 2.85 ng/mL, interquartile range (IQR) 3.52 versus median 1.22 ng/mL, IQR 2.99, versus median 0.1, IQR 0.09, p<0.001). Increased MIF levels were associated with CRP and IL-6 levels and correlated with troponin I (TnI) release (spearman rank coefficient: 0.31, p<0.001). Patients with ACS due to plaque rupture showed significantly higher plasma levels of MIF than patients with flow limiting stenotic lesions (p = 0.002).To our knowledge this is the first study, demonstrating enhanced expression of MIF in ACS. It is associated with established inflammatory markers, correlates with the extent of cardiac necrosis marker release after PCI and is significantly increased in ACS patients with “culprit” lesions. Further attempts should be undertaken to characterize the role of MIF for risk assessment in the setting of ACS

Results of univariate analysis of covariance (ANCOVA) for MIF and possible confounders in symptomatic CAD.

†<p>Hyperlipidemia was defined as triglycerides ≥175 mg/dl and/or LDL-cholesterol≥100 mg/dl and/or taking any of lipid lowering drugs.</p><p>ASA: aspirin.</p

Association of inflammatory markers IL-6, RANTES, MCP-1 and CRP with MIF levels in the study cohort.

<p>Association of inflammatory markers IL-6, RANTES, MCP-1 and CRP with MIF levels in the study cohort.</p

Correlation of the extent of maximum TnI release after PCI in the study cohort.

<p>Correlation of the extent of maximum TnI release after PCI in the study cohort.</p

Boxplots showing MIF-levels according to acuity of CAD compared with healthy volunteers.

<p>Boxplots showing MIF-levels according to acuity of CAD compared with healthy volunteers.</p

Baseline characteristics of the studied patients stratified according to median of MIF levels.

*<p>mean value ± standard deviation.</p>†<p>Hyperlipidemia was defined as triglycerides ≥175 mg/dl and/or LDL-cholesterol≥100 mg/dl and/or taking any of lipid lowering drugs.</p><p>ASA: aspirin.</p

Patients with ACS due to plaque rupture showed higher plasma levels of MIF than patients with flow limiting stenotic lesions in coronary angiography.

<p>Patients with ACS due to plaque rupture showed higher plasma levels of MIF than patients with flow limiting stenotic lesions in coronary angiography.</p