Die Bedeutung von Galectin-3 als Biomarker bei Patienten mit terminaler Herzinsuffizienz und mechanischer Herz-Kreislauf-Unterstützung

Die Zielsetzung der vorliegenden Dissertation war die Erforschung der prädiktiven Bedeutung des Biomarkers bei terminal herzinsuffizienten Patienten prä Ventricular Assist Device (VAD)-Implantation in Verbindung mit anderen etablierten klinischen Parametern. Die VAD-Kandidaten wiesen präoperativ signifikant höhere Galectin-3-Plasmakonzentrationen auf als die Kontrollgruppe. Die Cox-Regressions-Analyse zeigte, dass das Plasma-Galectin-3 kein unabhängiger Prädiktor für das Versterben am VAD ist. Patienten in den höheren Risikogruppen wiesen jedoch erhöhte Galectin-3-Werte auf. Eine Differenzierung der VAD-Typen in low-, intermedium- und high-risk Systeme zeigte bei einem Cut-off-Wert von 17 ng/ml für das Galectin-3 durchaus eine Assoziation mit dem Überleben am VAD in der low- und medium-risk Gruppe. Galectin-3-mRNA und Protein waren nachweisbar im Myokard. Für die Galectin-3-Plasmakonzentrationen bei VAD-Kandidaten spielt die myokardiale Expression des Lektins allerdings keine Rolle

Microparticle-Induced Coagulation Relates to Coronary Artery Atherosclerosis in Severe Aortic Valve Stenosis

<div><p>Background</p><p>Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification.</p><p>Methods</p><p>In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation.</p><p>Results</p><p>Patients with CAC score below the median were classified as patients with <i>low</i> CAC, patients with CAC Score above the median as <i>high</i> CAC. In patients with <i>high</i> CAC compared to patients with <i>low</i> CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with <i>high</i> and <i>low</i> CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation.</p><p>Conclusion</p><p>In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification.</p></div

Microparticle-Induced Coagulation Relates to Coronary Artery Atherosclerosis in Severe Aortic Valve Stenosis

Background Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification. Methods In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation. Results Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation. Conclusion In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification.</p

Aortic Valve Calcification (AVC) was not associated with Coronary Artery Calcification (CAC).

<p>(A) AVC did not differ between patients with <i>high</i> CAC compared to patients with <i>low</i> CAC. Data are presented as minimum and maximum (crosses), interquartile range from 25 to 75% (box), mean (square), and median (line) in a box plot. (B) AVC did not correlate with CAC.</p

Effectors of MP-induced thrombin generation by multivariate regression analysis.

<p>CD41⁺ PMPs predict MP-induced thrombin generation in a model using CD62E⁺ EMPs, CD31⁺/CD41^- EMPs and CD144⁺ EMPs.</p

Physiological Parameters.

<p>Physiological Parameters.</p

Patients‘ characteristics.

<p>Patients‘ characteristics.</p

Univariate Correlation analysis for the association between MP-induced thrombin generation and endothelial function (FMD) with circulating MPs, CAC Score and AVC Score.

<p>Univariate Correlation analysis for the association between MP-induced thrombin generation and endothelial function (FMD) with circulating MPs, CAC Score and AVC Score.</p

Enhanced plasma thrombin generation and MP-induced thrombin generation in patients with high CAC.

<p>(A) In patients with high CAC compared to patients with low CAC TATc level as a marker of thrombin generation in plasma were higher. (C) TATc level correlated with CAC Score. (B) MP-induced thrombin generation was higher in patients with <i>high</i> CAC compared to patients with <i>low</i> CAC. The kinetic of thrombin generation was assessed by measuring its specific activity on the thrombin substrate at different time points (0–10 min). Data are shown as MW±SE (D) MP-induced thrombin generation correlated with CAC Score. * indicates significant difference of the mean.</p