MicroRNA miR-29b regulates diabetic aortic remodeling and stiffening.

Schellinger IN, Wagenhaeuser M, Chodisetti G, Mattern K, Dannert A, Petzold A, Jakubizka-Smorag J, Emrich F, Haunschild J, Schuster A, Schwob E, Schulz K, Maegdefessel L, Spin JM, Stumvoll M, Hasenfuss G, Tsao PS, Raaz U (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Molecular Therapy - Nucleic Acids Elsevier (Cell Press)

Book Volume: 24

Pages Range: 188-199

DOI: 10.1016/j.omtn.2021.02.021

Abstract

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.

Involved external institutions

Universitätsklinikum Göttingen DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE) HELIOS Kliniken DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Stanford University US United States (USA) (US) Universität Leipzig DE Germany (DE)

How to cite

APA:

Schellinger, I.N., Wagenhaeuser, M., Chodisetti, G., Mattern, K., Dannert, A., Petzold, A.,... Raaz, U. (2021). MicroRNA miR-29b regulates diabetic aortic remodeling and stiffening. Molecular Therapy - Nucleic Acids, 24, 188-199. https://doi.org/10.1016/j.omtn.2021.02.021

MLA:

Schellinger, Isabel N., et al. "MicroRNA miR-29b regulates diabetic aortic remodeling and stiffening." Molecular Therapy - Nucleic Acids 24 (2021): 188-199.

BibTeX: Download