Endotheliale Dysfunktion: Pathophysiologie, Diagnostik und prognostische Bedeutung

Zusammenfassung

Die endotheliale Dysfunktion ist das erste klinisch fassbare Substrat für die Entwicklung einer Atherosklerose. Sie kann invasiv im Koronarkreislauf mit Hilfe der intrakoronaren Acetylcholininfusion, aber auch peripher, nicht invasiv, beispielsweise mit Hilfe der Ultraschall-gesteuerten Bestimmung der flussabhängigen Dilatation der Arteria brachialis bestimmt werden. Neuere Methoden, die aktuell in der Testphase sind, sind die Fingerpulsplethysmografie sowie die Pulswellenreflektion als Marker der vaskulären Steifigkeit (Stiffness), Parameter die entscheidend durch den funktionellen Zustand des Endothels bestimmt werden. Zu kardiovaskulären Risikofaktoren, die zur Ausbildung einer endothelialen Dysfunktion führen, zählen arterielle Hypertonie, Diabetes mellitus, Hypercholesterinämie, chronisches Rauchen, und familiäre Disposition. Die akute intraarterielle oder orale Gabe einer hohen Vitamin C-Dosis ist in der Lage, die endotheliale Dysfunktion zu korrigieren, was als Nachweis für die herausragende Rolle von reaktiven Sauerstoffspezies als Verursacher der endothelialen Dysfunktion gewertet wird. Enzymatische Quellen der vermehrten Radikalbildung sind Enzyme wie die vaskuläre NADPH-Oxidase, eine dysfunktionelle, entkoppelte endotheliale NO-Synthase, mitochondriale Atmungskettenenzyme, die Cyclooxygenase und die Xanthinoxidase.

Neuere Untersuchungen belegen, dass die endotheliale Dysfunktion in koronaren und peripheren Leitungs- und Widerstandsgefäßen bei Patienten mit einer bekannten koronaren Herzerkrankung, mit einer arteriellen Hypertonie oder mit einer peripheren arteriellen Verschlusserkrankung eine prognostische Bedeutung besitzt. Die Bedeutung der endothelialen Dysfunktion im Bereich der Primärprävention ist unklar. Sie wird in der zurzeit laufenden Gutenberg-Herzstudie untersucht.

Summary

The endothelium plays a crucial role in the regulation of vascular tone. Recent studies have indicated that endothelial dysfunction develops in the presence of cardiovascular risk factors such as hypertension, diabetes mellitus, hypercholesterolemia and in chronic smokers, as well as in patients with a family history of cardiovascular disease. It has now been established that endothelial dysfunction represents the first indicator of vascular damage. Endothelial function can be assessed in coronary and peripheral conductance and resistance vessels by means of invasive and noninvasive (ultrasound-guided) methods such as intracoronary infusion of acetylcholine, the endothelium-dependent vasodilator. It is interesting that endothelial dysfunction in the presence of cardiovascular risk factors can be almost completely corrected by the acute administration of antioxidants such as vitamin C, pointing to a crucial role of reactive oxygen species in mediating this phenomenon. Superoxide producing enzymes involved in the increased production of reactive oxygen species include NADPH oxidase, nitric oxide synthase in the uncoupled state, mitochondrial superoxide sources, cyclooxygenase and xanthine oxidase. Recent studies indicate that the endothelial dysfunction found in coronary and peripheral conductance and resistance vessels provide prognostic information about future cardiovascular events. The role of endothelial dysfunction in the setting of primary prevention is not yet clear, but is being investigated in the current Gutenberg Heart Study.

Schlüsselwörter

Endothel - Endotheliale Dysfunktion - Oxidativer Stress - Reaktive Sauerstoffspezies - Stickstoffmonoxid - Endotheliale Progenitorzellen

Keywords

endothelium - endothelial dysfunction - oxidative stress - reactive oxygen species - nitric oxide - endothelial progenitor cells

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