TY  - JOUR
A1  - Schellinger, Isabel N.
A1  - Wagenhäuser, Markus
A1  - Chodisetti, Giriprakash
A1  - Mattern, Karin
A1  - Dannert, Angelika
A1  - Petzold, Anne
A1  - Jakubizka-Smorag, Joanna
A1  - Emrich, Fabian Christoph
A1  - Haunschild, Josephina
A1  - Schuster, Andreas
A1  - Schwob, Elisabeth
A1  - Schulz, Kei
A1  - Mägdefessel, Lars
A1  - Spin, Joshua M.
A1  - Stumvoll, Michael
A1  - Hasenfuß, Gerd
A1  - Tsao, Philip S.
A1  - Raaz, Uwe
T1  - MicroRNA miR-29b regulates diabetic aortic remodeling and stiffening
T2  - Molecular Therapy - Nucleic Acids
N2  - 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.
KW  - diabetes mellitus
KW  - arterial stiffness
KW  - microRNA
KW  - non-coding RNA
KW  - extracellular matrix
KW  - collagen
KW  - elastin
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73776
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-737764
SN  - 2162-2531
N1  - 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.).
VL  - 24
SP  - 188
EP  - 199
PB  - Nature Publ. Group
CY  - New York, NY
ER  -