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Pathomorphologie der koronaren Atherosklerose

Pathomorphologic classification of coronary atherosclerosis

  • Koronare Atherosklerose — Funktionelle Konsequenzen
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Zusammenfassung

Das „American Heart Association Committee on Vascular Lesions” empfiehlt die im folgenden vorgestellte morphologische Klassifikation atherosklerotischer Plaques, basierend auf Vorschlägen von H. C. Stary. Diese Stadieneinteilung wurde an einer großen Serie von Autopsien erarbeitet, die eine Beobachtung der „natürlichen” Entwicklung von Plaques an, bestimmten Prädilektionsstellen der Atherosklerose im Bereich der Koronarien von ihren symptomlosen Frühstadien bis zu klinisch symptomatischen Läsionen ermöglichte. Der atherosklerotische Prozeß wird in fünf Phasen eingeteilt, die möglicherweise dem natürlichen zeitlichen Verlauf der Erkrankung entsprechen. Jede Phase ist durch Plaques mit charakteristischer Morphologie gekennzeichnet. Die Klassifikation bietet somit ein Spektrum typischer Morphologien, mit denen klinische Untersuchungsergebnisse korreliert werden können.

Aus der Plaquemorphologie wird deutlich, daß es sich bei der Atherosklerose um eine chronisch entzündliche Erkrankung der Gefäßintima handelt, die vergleichbar ist mit anderen chronisch entzündlichen Prozessen und Wundheilungsvorgängen. Klinische Komplikationen entstehen durch entzündungsbedingte Endothelerosionen und Plaquerupturen mit konsekutiver Thrombose. Rupturierte und rupturgefährdete Plaques sind gekennzeichnet durch: ein „lipid core”, das mehr als 40% des Plaquevolumens einnimmt, eine hohe Makrophagendichte, eine geringe Dichte an glatten Muskelzellen, eine dünne Deckplatte, einen geringen Gehalt an Kollagenfasern und eine hohe Expression von „tissue factor”

Die chronisch entzündlichen Prozesse innerhalb des Atheroms sind offenbar jedoch nicht nur für Plaqueinstabilität verantwortlich, sondern auch für die lokale koronare Hyperreaktivität im Bereich symptomatischer Gefäßstenosen. In diesem Zusammenhang spielt Endothelin 1 (ET-1), ein stark vasokonstriktorisch wirkendes Peptid, offenbar eine besondere Rolle. Wie unsere Untersuchungen zeigen, wird ET-1 lokal in der Wand atherosklerotischer Gefäße gebildet und kommt vor allem in Plaqueregionen mit starker chronischer Entzündung vor. Durch die semiquantitative Analyse der ET-1 IR wurde deutlich, daß in Plaques von Patienten mit akuten Koronarsyndromen signifikant mehr ET-1 vorhanden ist als in Plaques von Patienten mit stabiler Angina pectoris. Der erhöhte ET-1-Gehalt von instabilen atheroskerotischen Plaques ist von Vorteil, da er hilft, die Gefäßwand nach einer Plaqueruptur zu stabilisieren, indem ET-1 die Wundheilung nach Plaqueruptur unterstützt. Er ist nachteilig, da er offenbar zur Auslösung von Koronarspasmen beiträgt und das Fortschreiten der Atherosklerose begünstigt. Die Einführung von ETA-ETA/ETB- und ETB-Rezeptor-Antagonisten bietet eine direkte und neue Therapiemöglichkeit, welche die Rolle von ET-1 in der Pathophysiologie der akuten Koronarsyndrome weiter definieren wird. Bislang fehlen allerdings noch klinische Daten zur Wirkung dieser Substanzen bei akuten Koronarsyndromen oder vasospastischer Angina.

Summary

The “American Heart Association Committee on Vascular Lesions” suggests the following morphologic classification of atherosclerotic plaques: the classification is based on large autopsy studies facilitating the assessment of the natural course of atherosclerotic lesions at precisely defined progression prone areas of the coronary tree from their clinically silent beginning to the stage where they produce symptoms. Lesion evolution is divided in 5 phases reflecting the possible time course of plaque development. Each phase is characterized by plaques with a distinctive morphology. The classification offers a framework of typical morphologies which the results of clinical investigations may be related to.

Looking at the plaque composition, it is readily conceivable that atherosclerosis shares many characteristics with the general pathology of chronic inflammation and wound healing. Clinical symptoms e. g. acute coronary syndroms, arise from inflammation-mediated endothelial erosion and/or plaque rupture with ensuing coronary thrombosis. Advanced or complicated plaques are composed of different kinds of constituents in varying propotions. However, plaques at risk display a large lipid core occupying more than 40% of the plaque’s volume, increased numbers of macrophages, reduced numbers of smooth muscle cells, an increased expression of tissue factor, and a thin plaque cap.

Functionally, active plaques are characterized by a locally enhanced vasoreactivity with evidence coming from our own recent investigations that localised chronic inflammatory processes within the atherosclerotic plaque are responsible not only for the plaque rupture itself, but also for the hyperreactivity of these vessels to vasoconstrictor stimuli. In this context endothelin 1 (ET-1), a very potent vasoconstrictor peptide, may play an important role. ET-1 was originally reported to be produced by endothelial cells and to act locally in a paracrine fashion to regulate vascular tone. However, further studies have clarified that ET-1 is not only produced by endothelial cells but also by human inflammatory cells suggesting a role for ET-1 in inflammatory processes. Additionally, ET-1 displays a potent mitogenic activity. We examined immunohistochemically the presence of ET-1 in coronary plaque tissue obtained by directional coronary atherectomy. ET-1 immunoreactivity preferentially localized in plaque components indicative of a chronic inflammatory process. In addition, semiquantitative analysis of ET-1-like immunoreactivity revealed significantly higher staining grades in active coronary lesions compared with nonactive lesions. The increased ET-1 content in active coronary lesions may be beneficial to the stabilization of the vessel wall after plaque rupture and disadvantageous because it may lead to vasospasm and to the progression of atherosclerosis.

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    Christian Ihling

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Ihling, C. Pathomorphologie der koronaren Atherosklerose. Herz 23, 69–77 (1998). https://doi.org/10.1007/BF03044538

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