Therapeutisches Potenzial der nicht kodierenden RNAs für die akute und chronische Myokardischämie

Zusammenfassung

Ein Myokardinfarkt führt unter anderem zum Zelltod von Kardiomyozyten, dem eine mit Fibrose und Remodeling der Ventrikel verbundene Verletzungsreaktion des Herzens folgt. Nicht kodierende RNAs, insbesondere microRNAs, zeigen nach einem Infarkt bekanntlich verschiedene Aktivitäten im Herzen und steuern Verletzungsreaktionen und die Reparatur, indem sie den Tod der Kardiomyozyten, das Gefäßwachstum und die Herzfibrose beeinflussen. Zusätzlich können mehrere microRNAs moduliert werden, um die Herzregeneration zu beeinflussen. Derzeit werden in ersten Phase-I-Studien spezifische microRNA-Inhibitoren für ausgewählte microRNAs, sogenannte antimiRs, zur therapeutischen Anwendung am Menschen getestet. Neuere Studien weisen außerdem darauf hin, dass auch die weniger gut untersuchten langen nicht kodierenden RNAs gezielt beeinflusst werden können, um die Herzfunktion nach Infarkt zu verbessern. Der vorliegende Artikel fasst neuartige Ansätze zusammen, die auf nicht kodierende RNAs als therapeutische Option zur Förderung der Herzreparatur und -regeneration abzielen.

Abstract

Myocardial infarction leads to an initial cell death of cardiomyocytes that is followed by injury response associated with fibrosis and remodeling of the ventricle. Non coding RNAs, particularly microRNAs, are well known to exhibit various activities in the heart after injury and control the injury responses and repair by affecting cardiomyocyte death, vascular growth, and cardiac fibrosis. In addition, several microRNAs may be modulated to affect cardiac regeneration. MicroRNA inhibitors directed against specific microRNAs, so called antimiRs, are currently tested in first human Phase I studies. In addition, recent studies suggest that long non coding RNAs, although less well studied, might be targetable for improving cardiac function. The current article summarizes novel approaches targeting non coding RNAs as therapeutic option to promote cardiac repair and regeneration.

Was ist wichtig?

Nicht kodierende RNAs haben wesentliche Funktionen im Herz. Präklinische Studien zeigen, dass die gezielte Beeinflussung von kleinen, nicht kodierenden RNAs, genannt microRNAs, eine neue Therapieoption zur Behandlung von Herzinfarkt oder Herzmuskelschwäche darstellt. Aktuell werden solche Ansätze in ersten klinischen Studien getestet.

Schlüsselwörter

Herzinsuffizienz - Therapie - microRNAs - Myokardinfarkt - nicht kodierende RNAs

Key words

heart failure - therapy - microRNAs - myocardial infarction - non coding RNAs

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