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Die Rolle der Ribonuklease 1 und des Ribonuklease-Inhibitors 1 in der thorakoabdominellen Aortenchirurgie

Studiendesign einer Pilotstudie

Role of ribonuclease 1 and ribonuclease inhibitor 1 in thoracoabdominal aortic surgery

Study design of a pilot study

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Zusammenfassung

Eine gefürchtete Komplikation in der offenen und endovaskulären thorakoabdominellen Aortenchirurgie stellt die systemische Inflammationsreaktion und das damit assoziierte Multiorganversagen dar. Da trotz intensiver Forschung keine kausalen Therapeutika zur Eindämmung dieser postoperativen Komplikation etabliert werden konnten, ist die Identifizierung und Evaluation neuer therapeutischer Zielstrukturen für die betroffenen Patienten von entscheidender Bedeutung. Sowohl der hohe Gewebeschaden bei der offenen Behandlungsmethode als auch das Postimplantationssyndrom (PIS) nach endovaskulärer TAAA-Behandlung resultieren in einer Freisetzung von endogenen „damage-associated molecular patterns“ (DAMPs), wie zum Beispiel extrazelluläre Ribonukleinsäuren (RNA), die die systemische Inflammationsreaktion induzieren und aufrechterhalten. Ribonukleasen (RNasen) gehören der Gruppe endogener antimikrobieller Peptide an. Als Bestandteil des angeborenen Immunsystems modulieren RNasen die Immunreaktion auf körperfremde Pathogene sowie endogene DAMPs. Der Ribonuklease-Inhibitor 1 (RNH1) stellt den Antagonisten der RNase 1 dar. Dieser wird von verschiedenen Geweben exprimiert und inhibiert die RNase 1. Die Rolle der RNase 1 sowie des RNH1 als neuer, additiver Therapieansatz in dem inflammationsassoziierten Multiorganversagen nach chirurgischer thorakoabdominellen Aortenaneurysma- (TAAA-)Sanierung ist bisher jedoch ungeklärt. Ziel der geplanten Pilotstudie ist es daher, die Rolle der RNase 1 sowie des RNH1 als eine neue mögliche therapeutische Zielstruktur und/oder Biomarker in der offenen und endovaskulären thorakoabdominellen Aortenchirurgie und der damit assoziierten Inflammationsreaktion zu analysieren.

Abstract

A feared complication in open and endovascular thoracoabdominal aortic surgery is the systemic inflammatory response and associated multiorgan failure. As no causal therapeutic agents for suppression of this postoperative complication could be established despite intensive research, the identification and evaluation of new therapeutic target structures are crucial for the patients. The significant tissue damage during open surgery and the post-implantation syndrome (PIS) after endovascular thoracoabdominal aortic aneurysm (TAAA) repair result in the release of endogenous damage-associated molecular patterns (DAMP), such as extracellular ribonucleic acid (RNA), which induce and maintain the systemic inflammatory response. Ribonucleases (RNases) belong to the group of endogenous antimicrobial peptides. As a component of the innate immune system, RNases modulate the immune response to foreign pathogens and endogenous DAMPs. Ribonuclease inhibitor 1 (RNH1) represents the antagonist of RNase 1; however, the role of RNase 1 and RNH1 as a new additive treatment approach in systemic inflammation-associated multiorgan failure after surgical TAAA repair is still unclear. Therefore, the aim of the proposed pilot study is to analyze the role of RNase 1 and RNH1 as a new potential treatment target structure and/or biomarker in open and endovascular thoracoabdominal aortic repair and the associated inflammatory response.

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Authors and Affiliations

  1. Klinik für Operative Intensivmedizin und Intermediate Care, Uniklinik RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Deutschland

    E. Zechendorf, T.-P. Simon, G. Marx &  L. Martin MHBA

  2. European Vascular Center Aachen-Maastricht, Klinik für Gefäßchirurgie, Uniklinik RWTH Aachen, Aachen, Deutschland

    A. Gombert & D. Kotelis

Authors
  1. E. Zechendorf
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  2. A. Gombert
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  3. D. Kotelis
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  4. T.-P. Simon
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  5. G. Marx
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  6. L. Martin MHBA
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Correspondence to L. Martin MHBA.

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Interessenkonflikt

E. Zechendorf, A. Gombert, D. Kotelis, T.-P. Simon, G. Marx und L. Martin geben an, dass kein Interessenkonflikt besteht.

Alle beschriebenen Untersuchungen am Menschen oder an menschlichem Gewebe wurden mit Zustimmung der internen Ethikkommission der Uniklinik RWTH Aachen (EK004/14), im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor.

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Zechendorf, E., Gombert, A., Kotelis, D. et al. Die Rolle der Ribonuklease 1 und des Ribonuklease-Inhibitors 1 in der thorakoabdominellen Aortenchirurgie. Gefässchirurgie 25, 232–235 (2020). https://doi.org/10.1007/s00772-020-00655-y

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  • DOI: https://doi.org/10.1007/s00772-020-00655-y

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