Die instabile Karotisstenose

Zusammenfassung

Dieser Artikel informiert über die aktuelle Datenlage bezüglich der pathoanatomischen Merkmale und der möglichen pathophysiologischen Mechanismen, die zu einer Destabilisierung einer hochgradigen Stenose der Arteria carotis interna im extrakraniellen Bifurkationsbereich führen können. Neben dem Vorhandensein zerebral-ischämischer Symptome spielt die so genannte zerebrale Mikroemboliedetektion eine große Rolle bei der präoperativen Charakterisierung und Einteilung der Instabilität. Systematische pathoanatomische Arbeiten zeigten, dass die instabile Karotisplaque im Wesentlichen gekennzeichnet ist durch Plaqueruptur und intraluminale Thrombusformation. Hingegen gibt es ca. 50% der instabilen Plaque, die entweder nur eine Thrombose auf intakter Oberfläche zeigen oder pathoanatomisch nicht die typischen Zeichen der Plaqueruptur aufweisen. Ganz eindeutig ist die instabile Karotisplaque gekennzeichnet durch eine signifikant erhöhte Infiltration mit Entzündungszellen (T-Lymphozyten und Makrophagen), die im Wesentlichen im lumenabwärtsgerichteten Teil der fibrotischen Deckplatte (d. h. dem nekrotischen Kern assoziiert) lokalisiert sind. Von Makrophagen sezerniert findet sich eine erhöhte Expression matrixdegradierender Enzyme (z. B. MMP-9), ebenso zeigt sich eine erhöhte Thombogenität des atherosklerotischen Materials, hauptsächlich vermittelt durch überexprimierten Gewebefaktor. Ein weiteres Kennzeichen der instabilen Plaque ist eine erhöhte Rate von Apoptosen glatter Muskelzellen der fibrotischen Deckplatte. Bakterielle Erreger (z. B. Chlamydia pneumoniae) spielen wahrscheinlich bei der Destabilisierung keine Rolle, da keine eindeutige Assoziation zu den klinischen Markern der Instabilität gezeigt werden konnte. Die exakte pathomorphologische und pathophysiologische Charakterisierung der instabilen Karotisplaque ermöglicht neue Einsichten in Mechanismen der Destabilisierung der humanen Atherosklerose und eröffnet eine Perspektive zur Testung verschiedener pharmakologischer Ansätze zur Beeinflussung der Plaque-Instabilität im Allgemeinen.

Summary

The occurrence of cerebral or retinal ischemic symptoms ipsilateral to high-grade internal carotid artery (ICA) stenosis indicates a status of instability with a substantial risk for future major stroke. Additionally, the detection of microembolic signals downstream of ICA stenosis is predictive for future cerebral ischemia in asymptomatic and symptomatic patients. There is substantial evidence that in unstable ICA stenosis plaque rupture and thrombus formation are the most frequent pathoanatomic findings. In contrast, in nearly the half of unstable carotid plaques the lumen surface appears to be intact. Within plaque tissue, the unstable plaque is mainly characterized by a substantial amount of inflammatory cell (i. e. macrophages, T-cells) infiltration. These cells are mainly localized in the fibrous cap near the necrotic core. Produced by macrophages, matrix degrading enzymes (e. g. MMP-9) are overexpressed in the unstable ICA stenosis. Thrombogenicity is mainly determined by the local concentration of activated tissue factor, also expressed by inflammatory cells. Furthermore, a significantly higher rate of apoptotic smooth muscle cells can be found within the fibrous cap of instable carotid stenoses. Whether infection with Chlamydia pneumoniae contribute to instability is unlikely, because a positive association to clinical instability has not been shown up to now. The exact and detailed characterization of the unstable ICA plaque and the correlation of different biological mechanisms to clinical instability may offer the possibility to use it as a human model of unstable atherosclerosis in general and to test the efficacy of new developed anti-atherosclerotic pharmaceutical agents.

Schlüsselwörter

Arteria carotis interna - Atherosklerose - Schlaganfall

Keywords

Arteria carotis interna - atherosclerosis - stroke

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