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Genetic risk factors and restenosis after percutaneous coronary interventions

Genetische Risikofaktoren und Restenose nach perkutanen Koronarinterventionen

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Abstract

Restenosis is the major limitation of percutaneous coronary interventions. Depending on the form of intervention and patients' characteristics, 20 to 50% of the treated patients incur significant restenosis. Restenosis is caused by a complex and only partially understood cascade of events. Thrombus formation at the injury site, formation of the neointima as a result of the migration and proliferation of smooth muscle cells (SMC) and extracellular matrix production, as well as constrictive remodeling of the vessel wall contribute by a variable degree to restenosis.

Restenosis is not a random event but it affects selectively a certain subset of patients. These patients have some peculiar characteristics that help to identify the presence of a higher risk for restenosis. Conventional patient-related factors account only for a relatively small portion of the predictive power, much more contribution comes from lesion and procedural characteristics. There is increasing evidence that inherited factors may explain at least part of the excessive risk for restenosis observed in certain patients.

Evidence exists that gene polymorphisms may lead to quantitative or functional alterations of the respective gene products. Recent studies have also found significant associations between several polymorphic alleles encoding for proteins with a relevant role in the process of lumen renarrowing and restenosis after percutaneous coronary interventions. The best studied polymorphisms in this regard are those of the genes encoding for angiotensin-converting enzyme and platelet glycoprotein-IIIa. Completed or ongoing studies have focused on polymorphisms of genes encoding for proteins interfering with lipid metabolism, hemostasis, nitric oxide production, inflammatory mechanisms, SMC proliferation and matrix production. The results of this research will have considerable pathophysiological and therapeutical implications for the battle against restenosis.

Zusammenfassung

Die Restenose stellt heute die wesentliche Limitation perkutaner Koronarinterventionen dar. Abhängig von der Art der Intervention und von Patientencharakteristika entwickeln 20 bis 50% der Patienten eine signifikante Restenosierung. Eine komplexe, bislang nur teilweise aufgeklärte Kaskade von Ereignissen führt zur erneuten Lumeneinengung. Thrombusformation an der interventionsbedingten Verletzungsstelle, Neointimabildung, Folge der Migration und Proliferation glatter Gefäßmuskelzellen und die Produktion extrazellulärer Matrix sowie ein negatives (konstriktives) Remodelling der Gefäßwand tragen in unterschiedlichem Ausmaß zur Restenose bei.

Ihre Entwicklung ist kein Ereignis, das zufällig bei einem Teil der Patienten auftritt, vielmehr ist selektiv eine bestimmte Subpopulation betroffen. Diese Patienten weisen einige Besonderheiten auf, die dazu beitragen, ein erhöhtes Restenoserisiko zu charakterisieren. Dabei ist die Bedeutung konventioneller, patientenbezogener Faktoren für die Prädiktion einer Restenose relativ gering, während läsionsbezogene und prozedurale Charakteristika sehr viel stärkere Prädiktoren sind. Darüber hinaus mehren sich die Hinweise, daß genetische Faktoren zumindest teilweise das exzessive Restenoserisiko bestimmter Patienten erklären können.

Genpolymorphismen können zu quantitativen oder funktionellen Veränderungen des jeweiligen Genprodukts führen. Neuere Untersuchungen zeigten eine signifikante Assoziation zwischen Restenose nach Koronarintervention und verschiedenen polymorphen Allelen, die für Proteine kodieren, die beim Restenoseprozeß von Relevanz sind. Diesbezüglich am besten untersucht sind Polymorphismen jener Gene, die für das Angiotensinkonversionsenzym und für thrombozytäres Glycoprotein IIIa kodieren.

Eine Vielzahl abgeschlossener und noch laufender Studien konzentriert sich auf Polymorphismen in Genen, die für Proteine kodieren, welche mit dem Lipidmetabolismus, der Hämostase, der NO-Produktion, den inflammatorischen Mechanismen, der Proliferation glatter Gefäßmuskelzellen und der Matrixproduktion interferieren. Die Ergebnisse dieser Forschung werden wesentliche pathophysiologische und therapeutische Implikationen für den Kampf gegen die Restenose haben.

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Authors and Affiliations

  1. Deutsches Herzzentrum München, Lazarettstraße 36, D-80636, München, Germany

    Adnan Kastrati MD, Josef Dirschinger & Albert Schömig

  2. Medizinische Klinik rechts der Isar, Technische Universität, Munich, Germany

    Albert Schömig

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  1. Adnan Kastrati MD
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  2. Josef Dirschinger
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  3. Albert Schömig
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Correspondence to Adnan Kastrati MD.

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Kastrati, A., Dirschinger, J. & Schömig, A. Genetic risk factors and restenosis after percutaneous coronary interventions. Herz 25, 34–46 (2000). https://doi.org/10.1007/BF03044122

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