Isabel N. Schellinger, Markus Wagenhäuser, Giriprakash Chodisetti, Karin Mattern, Angelika Dannert, Anne Petzold, Joanna Jakubizka-Smorag, Fabian Christoph Emrich, Josephina Haunschild, Andreas Schuster, Elisabeth Schwob, Kei Schulz, Lars Mägdefessel, Joshua M. Spin, Michael Stumvoll, Gerd Hasenfuß, Philip S. Tsao, Uwe Raaz
- Patients with type 2 diabetes (T2D) are threatened by excessive cardiovascular morbidity and mortality. While accelerated arterial stiffening may represent a critical mechanistic factor driving cardiovascular risk in T2D, specific therapies to contain the underlying diabetic arterial remodeling have been elusive. The present translational study investigates the role of microRNA-29b (miR-29b) as a driver and therapeutic target of diabetic aortic remodeling and stiffening. Using a murine model (db/db mice), as well as human aortic tissue samples, we find that diabetic aortic remodeling and stiffening is associated with medial fibrosis, as well as fragmentation of aortic elastic layers. miR-29b is significantly downregulated in T2D and miR-29b repression is sufficient to induce both aortic medial fibrosis and elastin breakdown through upregulation of its direct target genes COL1A1 and MMP2 thereby increasing aortic stiffness. Moreover, antioxidant treatment restores aortic miR-29b levels and counteracts diabetic aortic remodeling. Concluding, we identify miR-29b as a comprehensive—and therefore powerful—regulator of aortic remodeling and stiffening in T2D that moreover qualifies as a (redox-sensitive) target for therapeutic intervention.
MetadatenAuthor: | Isabel N. Schellinger, Markus WagenhäuserORCiDGND, Giriprakash ChodisettiGND, Karin MatternGND, Angelika Dannert, Anne PetzoldGND, Joanna Jakubizka-Smorag, Fabian Christoph EmrichGND, Josephina HaunschildGND, Andreas SchusterGND, Elisabeth Schwob, Kei Schulz, Lars MägdefesselORCiDGND, Joshua M. SpinORCiD, Michael StumvollORCiD, Gerd HasenfußORCiDGND, Philip S. TsaoORCiD, Uwe RaazGND |
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URN: | urn:nbn:de:hebis:30:3-737764 |
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DOI: | https://doi.org/10.1016/j.omtn.2021.02.021 |
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ISSN: | 2162-2531 |
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Parent Title (English): | Molecular Therapy - Nucleic Acids |
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Publisher: | Nature Publ. Group |
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Place of publication: | New York, NY |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/06/04 |
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Date of first Publication: | 2021/06/04 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2023/05/09 |
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Tag: | arterial stiffness; collagen; diabetes mellitus; elastin; extracellular matrix; microRNA; non-coding RNA |
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Volume: | 24 |
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Page Number: | 12 |
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First Page: | 188 |
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Last Page: | 199 |
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Note: | This work was supported by research grants from the Deutsche Forschungsgemeinschaft (Sche 2125/2-1 to I.N.S.); the University of Leipzig Medical Faculty (934300-022 to I.N.S.); the University of California Tobacco-Related Disease Research Program (T29IR06360 and 26IP-0041 to J.M.S.); and the German Center for Cardiovascular Research (DZHK) e.V. (81X3300104 to U.R.). |
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Institutes: | Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International |
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