Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus

• DOI: 10.1161/circresaha.115.306341
• Publication Date: 2015-07-25T03:45:05Z
• Authors: Uwe Raaz; Isabel N. Schelli...; Ekaterina Chernog...; Christina Warnecke; Yosuke Kayama; Kiril Penov; Jan K. Hennigs; Florian Salomons; Suzanne Eken; Fabian C. Emrich; Wei H. Zheng; Matti Adam; Ann Jagger; Futoshi Nakagami; Ryuji Toh; Kensuke Toyama; Alicia Deng; Michael Buerke; Lars Maegdefessel; Gerd Hasenfuß; Joshua M. Spin; Philip S. Tsao
• Keywords: RUNX2

Accelerated arterial stiffening is a major complication of diabetes mellitus with no specific therapy available to date.The present study investigates the role osteogenic transcription factor runt-related 2 (Runx2) as potential mediator and therapeutic target aortic fibrosis in mellitus.Using murine model type (db/db mice), we identify progressive structural that precedes onset hypertension. At same time, Runx2 aberrantly upregulated medial layer db/db aortae, well thoracic samples from patients mellitus. Vascular smooth muscle cell-specific overexpression transgenic mice increases expression its genes, Col1a1 Col1a2, leading stiffening. Interestingly, increased per se not sufficient induce calcification. Using vivo vitro approaches, further demonstrate regulated via redox-sensitive pathway involves direct interaction NF-κB promoter.In conclusion, this highlights previously unrecognized inducer vascular setting mellitus, promoting stiffness irrespective