Browsing by Subject "aortic aneurysm"

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    Molecular and Genetic Insights into Thoracic Aortic Dilation in Conotruncal Heart Defects
    (Frontiers Media SA, 2016) Kay, W. Aaron; Department of Medicine, IU School of Medicine
    Thoracic aortic dilation (AD) has commonly been described in conotruncal defects (CTDs), such as tetralogy of Fallot, double outlet right ventricle and transposition of the great arteries, and truncus arteriosus. Several theories for this have been devised, but fairly recent data indicate that there is likely an underlying histologic abnormality, similar to that seen in Marfan and other connective tissue disease. The majority of aortic dissection in the general population occurs after the age of 45 years, and there have been very few case reports of aortic dissection in CTD. Given advances in cardiac surgery and increasing survival over the past several decades, there has been rising concern that, as patients who have survived surgical correction of these defects age, there may be increased morbidity and mortality due to aortic dissection and aortic regurgitation. This review discusses the most recent developments in research into AD in CTD, including associated genetic mutations.
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    Targeting long non-coding RNA NUDT6 enhances smooth muscle cell survival and limits vascular disease progression
    (Cold Spring Harbor Laboratory, 2023-06-07) Winter, Hanna; Winski, Greg; Busch, Albert; Chernogubova, Ekaterina; Fasolo, Francesca; Wu, Zhiyuan; Bäcklund, Alexandra; Khomtchouk, Bohdan B.; Van Booven, Derek J.; Sachs, Nadja; Eckstein, Hans-Henning; Wittig, Ilka; Boon, Reinier A.; Jin, Hong; Maegdefessel, Lars; Biohealth Informatics, School of Informatics and Computing
    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.