Refine
Document Type
- Article (3)
Has Fulltext
- yes (3)
Is part of the Bibliography
- no (3)
Keywords
- ATM (1)
- Cnidium dubium (1)
- MT: Non-coding RNAs (1)
- abdominal aortic aneurysm (1)
- aortic aneurysm (1)
- apoptosis (1)
- atherosclerosis (1)
- biomarker (1)
- circular RNA (1)
- doxorubicin (1)
Institute
- Medizin (2)
Durch lebensraumtypkonforme Nutzung oder Pflege wird gewöhnlich die Erhaltung bestehender Brenndoldenwiesen erreicht. Die Entwicklung solcher Wiesen auf artenarmem Grünland ist deutlich aufwändiger. Zielarten der Brenndolden-Auenwiesen sind Brenndolde (Cnidium dubium), Gräben-Veilchen (Viola persicifolia), Wiesen-Schwertlilie (Iris sibirica), Kanten-Lauch (Allium angulosum), Nordisches Labkraut (Galium boreale) und Großer Wiesenknopf (Sanguisorba officinalis). Um Ausbreitungshemmnisse zu überwinden, besteht die Möglichkeit, die Entwicklung von artenreichen Brenndoldenwiesen durch Renaturierungsmaßnahmen zu fördern. Unter Renaturierung wird hier die Entwicklung von halbnatürlichen Grünlandgesellschaften verstanden. Dies wird auch als Revitalisierung bezeichnet. Im Rahmen des hier vorgestellten Projektes wird die Ausweitung von Brenndolden-Auenwiesen durch Übertragung von samenreichem Mahdgut auf artenarmes Grünland angestrebt. Das hier beschriebene Vorhaben (LPR 2008) erfolgt im Rahmen des Naturschutzgroßprojektes „Pflege- und Entwicklungsplan (PEP) für das Naturschutzgroßprojekt von gesamtstaatlich repräsentativer Bedeutung Mittlere Elbe“ (LPR 2005).
Long non-coding RNAs (lncRNAs) orchestrate various biological processes and regulate the development of cardiovascular diseases. Their potential therapeutic benefit to tackle disease progression has recently been extensively explored. Our study investigates the role of lncRNA Nudix Hydrolase 6 (NUDT6) and its antisense target fibroblast growth factor 2 (FGF2) in two vascular pathologies: abdominal aortic aneurysms (AAA) and carotid artery disease. Using tissue samples from both diseases, we detected a substantial increase of NUDT6, whereas FGF2 was downregulated. Targeting Nudt6 in vivo with antisense oligonucleotides in three murine and one porcine animal model of carotid artery disease and AAA limited disease progression. Restoration of FGF2 upon Nudt6 knockdown improved vessel wall morphology and fibrous cap stability. Overexpression of NUDT6 in vitro impaired smooth muscle cell (SMC) migration, while limiting their proliferation and augmenting apoptosis. By employing RNA pulldown followed by mass spectrometry as well as RNA immunoprecipitation, we identified Cysteine and Glycine Rich Protein 1 (CSRP1) as another direct NUDT6 interaction partner, regulating cell motility and SMC differentiation. Overall, the present study identifies NUDT6 as a well-conserved antisense transcript of FGF2. NUDT6 silencing triggers SMC survival and migration and could serve as a novel RNA-based therapeutic strategy in vascular diseases.
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.