Author + information
- Uwe Raaz,
- Isabel Schellinger,
- Karin Mattern,
- Lena Mattes,
- Joshua Spin,
- Andreas Schuster,
- Lars Maegdefessel,
- Gerd Hasenfuss and
- Philip Tsao
Background: Accelerated arterial stiffening is a common complication of type 2 diabetes that is patho-mechanistically linked to a severely increased cardiovascular risk in diabetic patients. Unfortunately, up to date specific strategies to effectively address diabetic vascular stiffening are elusive. The discovery of non-coding microRNAs (miRs) provides new opportunities for innovative therapeutical approaches. Specifically, microRNA-29b may potentially serve as a comprehensive regulator of vascular fibrosis as well as elastin breakdown, both contributing to diabetic arterial stiffness. This study was designed to investigate the role of miR-29b as potential mediator and therapeutic target of diabetic aortic stiffness.
Methods and Results: Ex vivo mechanical testing of thoracic aortae via pressure myography revealed increased aortic stiffness in diabetic db/db mice. Vascular stiffening was accompanied by increased elastin fragmentation and collagen deposition (EvG and Picrosirius Red staining). qRT-PCR, in-situ hybridization and immunohistochemistry revealed decreased expression of miR-29b and de-repression of target genes (Col1A1, COL3A1, MMP2, MMP9) in db/db mice compared to controls. Investigating the mechanistic significance of miR-29b for arterial stiffening, forced downregulation of miR-29b (via systemic LNA-miR-29b inhibitor application) results in enhanced elastin fragmentation, increased medial collagen deposition, and increased aortic stiffness. Conversely, miR-29b overexpression (using a in vivo-jetPEI approach) effectively contained diabetic aortic stiffening in db/db mice.
Conclusions: In conclusion, this study identifies miR-29b downregulation in diabetic vessels as a patho-mechanistic driver of vascular fibrosis and elastin fragmentation leading to increased arterial stiffness. Therapeutically, restoration of miR-29b is sufficient to prevent adverse arterial remodeling in the context of diabetes.
Moderated Poster Contributions
Vascular Medicine Moderated Poster Theater, Poster Hall, Hall C
Saturday, March 18, 2017, 1:30 p.m.-1:40 p.m.
Session Title: Uncovering the Intricacies of Vascular Function
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1228M-11
- 2017 American College of Cardiology Foundation