Abstract
Endothelial denudation of rat carotids with a balloon catheter leads to migration and proliferation of medial smooth muscle cells in the neointima. This experimental model of atherosclerosis was used in cholesterol-neutral, normotensive rats to study the effect of Lovastatin as an inhibitor of HMG-CoA(Hydroxymethylglutaryl-Coenzyme A)-reductase by morphometric analysis of arterial cross sections. Treatment with 30 mg/kg bodyweight/day Lovastatin leads to the formation of smaller neointimal thickenings than in the control group. The reduction is about 22%. Accordingly, the vessel lumina were larger — by 42%. This luminal enlargement was not only due to the reduced plaque growth, but also to a reduction in the persistent vessel contraction observed in the control group. This positive effect would indicate that the blood vessels are reacting better towards vessel relaxant factors in the presence of Lovastatin. The reduction in plaque growth, due to inhibition of mevalonate synthesis by Lovastatin, probably involves several intermediate steps, including an inhibition of farnesylation in the cell membrane and of the formation of isopentenyl groups, which result in an inhibition of DNA synthesis and cell proliferation.
Zusammenfassung
Restenosierung von Arterien nach perkutaner transluminaler Angioplastie ist nach wie vor ein Hauptproblem dieser Gefäßerweiterungsmethode. Mehrere Autoren nennen Neuverschlußraten von 16% bis 45%, die innerhalb eines halben Jahres nach chirurgischem Eingriff beobachtet worden sind [11, 12, 15, 16, 18, 22]. Die Ursachen der Restenosierung und des erneuten Gefäßverschlusses nach Ballonangioplastie sind erst wenig verstanden [19]. Plättchenaggregation und Thrombusbildung sowie anhaltende myointimale Proliferation tragen zur Neubildung von Läsionen bei [4, 8, 17]. Die Proliferation und Migration glatter Muskelzellen sowie die Überproduktion von Bindegewebe nach Arterienwandverletzung sind die wesentlichen Merkmale für das gefäßverengende Wachstum von neointimalem Gewebe.
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Völker, W., Faber, V., Brüning, T., Buddecke, E., Eckardt, H. (1992). Inhibition of mevalonate synthesis reduces neointimal outgrowth in balloon injured rat carotid arteries. In: Heinle, H., Schulte, H., Schaefer, H.E. (eds) Arteriosklerotische Gefäßerkrankungen. Vieweg+Teubner Verlag, Wiesbaden. https://doi.org/10.1007/978-3-663-19646-4_38
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DOI: https://doi.org/10.1007/978-3-663-19646-4_38
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