TY  - JOUR
A1  - Fasolo, Francesca
A1  - Winski, Greg
A1  - Li, Zhaolong
A1  - Wu, Zhiyuan
A1  - Winter, Hanna
A1  - Ritzer, Julia
A1  - Glukha, Nadiya
A1  - Roy, Joy
A1  - Hultgren, Rebecka
A1  - Pauli, Jessica
A1  - Busch, Albert Franz Jakob
A1  - Sachs, Nadja
A1  - Knappich, Christoph Magnus
A1  - Eckstein, Hans-Henning
A1  - Boon, Reinier
A1  - Paloschi, Valentina
A1  - Mägdefessel, Lars
T1  - The circular RNA Ataxia Telangiectasia Mutated regulates oxidative stress in smooth muscle cells in expanding abdominal aortic aneurysms
T2  - Molecular therapy. Nucleic acids
N2  - 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.
KW  - MT: Non-coding RNAs
KW  - circular RNA
KW  - abdominal aortic aneurysm
KW  - smooth muscle cells
KW  - oxidative stress
KW  - apoptosis
KW  - biomarker
KW  - ATM
KW  - doxorubicin
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/79093
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-790937
SN  - 2162-2531
VL  - 33
SP  - 848
EP  - 865
PB  - Elsevier
CY  - Amsterdam
ER  -