Abstract 13061: Vascular Smooth Muscle Cell-selective O-GlaNAcylation Protects Arteries Against Acute Injury
BACKGROUND: We previously demonstrated that acutely increasing protein O-GlcNAcylation via pharmacological approaches inhibited inflammation and neointima formation in balloon injured rat carotid arteries. The goal of this study was to use a novel bitransgenic mouse model with inducible, vascular smooth muscle cell (SMC)-selective overexpression of O-GlcNAcylation to test a direct cause-effect relationship between protein O-GlcNAcylation and vasoprotection..
METHODS AND RESULTS: SM22-rtTA mice that express the reverse tetracycline-controlled transactivator (rtTA) protein under the control of the murine SM22 promoter were bred with TRE-EGFP-NCOATGK mice that carry a dominant negative oga gene (NCOATGK) under the regulatory control of a tetracycline-responsive promoter element (TRE) to yield mice that carry both transgenes (SM-rtTA/NCOATGK). Littermates that only carry SM22-rt-TA were controls. In response to doxycycline (Dox), total O-GlcNAc-modified protein levels increased 2-fold in aorta of SM-rtTA/NCOATGK mice compared to vehicle (V)(Fig). Immunofluorescence staining with anti-enhanced green fluorescent (EGFP) antibody followed by Alex Fluoro 448-labeled secondary antibody revealed selective staining of SMCs in carotid artery of Dox-treated mice (Fig), indicating expression of chimeric EGFP-NCOATGK protein in vascular SMC. Neointimal formation in Dox-treated SM-rtTA/NCOATGK mice at 28 days post carotid ligation was significantly less than in V-treated SM-rtTA/NCOATGK mice or Dox-treated SM22-rtTA mice (Fig).
Conclusion: Selective overexpression of O-GlcNAc-modified protein in SMCs protects arteries against adverse remodeling in the setting of acute injury.
- © 2013 by American Heart Association, Inc.