The circular RNA Ataxia Telangiectasia Mutated regulates oxidative stress in smooth muscle cells in expanding abdominal aortic aneurysms

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Francesca Fasolo - , Technische Universität München (Autor:in)
  • Greg Winski - , Karolinska Institutet (Autor:in)
  • Zhaolong Li - , Technische Universität München (Autor:in)
  • Zhiyan Wu - , Technische Universität München (Autor:in)
  • Hanna Winter - , Technische Universität München (Autor:in)
  • Julia Ritzer - , Technische Universität München (Autor:in)
  • Nadiya Glukha - , Technische Universität München (Autor:in)
  • Joy Roy - , Karolinska Institutet (Autor:in)
  • Rebecka Hultgren - , Karolinska Institutet (Autor:in)
  • Jessica Pauli - , Technische Universität München (Autor:in)
  • Albert Busch - , Klinik und Poliklinik für Viszeral- Thorax- und Gefäßchirurgie (Autor:in)
  • Nadja Sachs - , Technische Universität München (Autor:in)
  • Christoph Knappich - , Technische Universität München (Autor:in)
  • Hans-Henning Eckstein - , Technische Universität München (Autor:in)
  • Reinier A Boon - , Deutsches Zentrum für Herz-Kreislaufforschung (DZHK) (Autor:in)
  • Valentina Paloschi - , Technische Universität München (Autor:in)
  • Lars Maegdefessel - , Technische Universität München (Autor:in)

Abstract

An abdominal aortic aneurysm (AAA) is a pathological widening of the aortic wall characterized by loss of smooth muscle cells (SMCs), extracellular matrix degradation, and local inflammation. This condition is often asymptomatic until rupture occurs, leading to high morbidity and mortality rates. Diagnosis is mostly accidental and the only currently available treatment option remains surgical intervention. Circular RNAs (circRNAs) represent a novel class of regulatory non-coding RNAs that originate from backsplicing. Their highly stable loop structure, combined with a remarkable enrichment in body fluids, make circRNAs promising disease biomarkers. We investigated the contribution of circRNAs to AAA pathogenesis and their potential application to improve AAA diagnostics. Gene expression analysis revealed the presence of deregulated circular transcripts stemming from AAA-relevant gene loci. Among these, the circRNA to the Ataxia Telangiectasia Mutated gene (cATM) was upregulated in human AAA specimens, in AAA-derived SMCs, and serum samples collected from aneurysm patients. In primary aortic SMCs, cATM increased upon angiotensin II and doxorubicin stimulation, while its silencing triggered apoptosis. Higher cATM levels made AAA-derived SMCs less vulnerable to oxidative stress, compared with control SMCs. These data suggest that cATM contributes to elicit an adaptive oxidative-stress response in SMCs and provides a reliable AAA disease signature.

Details

OriginalspracheEnglisch
Seiten (von - bis)848-865
Seitenumfang18
FachzeitschriftMolecular therapy. Nucleic acids
Jahrgang33
PublikationsstatusVeröffentlicht - 12 Sept. 2023
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC10481153
Scopus 85169018563

Schlagworte

Ziele für nachhaltige Entwicklung

Bibliotheksschlagworte