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

Francesca Fasolo, Greg Winski, Zhaolong Li, Zhiyan Wu, Hanna Winter, Julia Ritzer, Nadiya Glukha, Joy Roy, Rebecka Hultgren, Jessica Pauli, Albert Busch, Nadja Sachs, Christoph Knappich, Hans Henning Eckstein, Reinier A. Boon, Valentina Paloschi, Lars Maegdefessel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Pages (from-to)848-865
Number of pages18
JournalMolecular Therapy - Nucleic Acids
Volume33
DOIs
StatePublished - 12 Sep 2023
Externally publishedYes

Keywords

  • ATM
  • MT: Non-coding RNAs
  • abdominal aortic aneurysm
  • apoptosis
  • biomarker
  • circular RNA
  • doxorubicin
  • oxidative stress
  • smooth muscle cells

Fingerprint

Dive into the research topics of 'The circular RNA Ataxia Telangiectasia Mutated regulates oxidative stress in smooth muscle cells in expanding abdominal aortic aneurysms'. Together they form a unique fingerprint.

Cite this