MicroRNA 29b-dependent mechanisms of arterial stiffness in diabetes.
Final Report Abstract
What is known: 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. Recently, microRNAs, a subspecies of so-called non-coding RNAs and their regulators such as circRNAs, have emerged as powerful regulators of gene expression that orchestrate diverse physiological and pathological processes. What the findings of this study add: The results of this project demonstrate that microRNA miR-29b is downregulated in human and murine diabetic aortae, and that miR-29b repression is a mechanistic driver of collagen deposition and elastin fragmentation, inducing arterial stiffening. As such, we were able to indentify miR-29b as a potential therapeutic target to attenuate or prevent diabetic aortic stiffening. What surprised us: In contrast to one of our project hypothesis, we could not verify another non-coding RNA, circular RNA circHIPK3, as an upstream regulator of miR-29b in diabetic tissues. However, we found that miR-29b acts as a redox-sensitive target in diabetic aortae, and that antioxidant intervention counteracts diabetic aortic remodeling and stiffening. This may be important for further translation of this preclinical research, as antioxidant agents are already widely available in the clinical setting.
Publications
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MicroRNA miR-29b regulates diabetic aortic remodeling and stiffening. Molecular Therapy - Nucleic Acids, 24, 188-199.
Schellinger, Isabel N.; Wagenhäuser, Markus; Chodisetti, Giriprakash; Mattern, Karin; Dannert, Angelika; Petzold, Anne; Jakubizka-Smorag, Joanna; Emrich, Fabian; Haunschild, Josephina; Schuster, Andreas; Schwob, Elisabeth; Schulz, Kei; Maegdefessel, Lars; Spin, Joshua M.; Stumvoll, Michael; Hasenfuß, Gerd; Tsao, Philip S. & Raaz, Uwe
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Unresolved Issues in RNA Therapeutics in Vascular Diseases With a Focus on Aneurysm Disease. Frontiers in Cardiovascular Medicine, 8.
Schellinger, Isabel N.; Dannert, Angelika R.; Mattern, Karin; Raaz, Uwe & Tsao, Philip S.
