Abstract
Abstract 14050: The Gut Flora Promotes Endothelial Dysfunction Through Vascular MicroRNA-204-mediated Down-regulation of Endothelial Sirtuin1
Circulation (New York, N.Y.), Vol.130(suppl_2)
11/25/2014
DOI: 10.1161/circ.130.suppl_2.14050
Abstract
The gut flora contributes to development of atherosclerosis. Endothelial dysfunction, one manifestation of which is impaired endothelium-dependent vasorelaxation, accompanies and promotes atherosclerotic vascular disease. Here we show that gut flora impair endothelium-dependent vasorelaxation by remotely up-regulating microRNA-204 (miR-204) which downregulates SIRTUIN1 (SIRT1) in the vascular wall. Microarray analysis in aortas of germ-free mice revealed a set of down-regulated microRNAs, including miR-204, which target SIRT1. Suppression of gut flora in mice with antibiotics in drinking water decreased aortic miR-204, increased aortic SIRT1, and improved endothelium-dependent vasorelaxation, effects that were reversed with discontinuation of antibiotics. In addition, miR-204 mimic impaired endothelium-dependent aortic vasorelaxation ex vivo. Moreover, high-fat diet feeding stimulated aortic miR-204, suppressed SIRT1, and impaired endothelial function, all of which were mitigated by administration of antibiotics, and reversed with stoppage of antibiotics. In contrast, antibiotics did not improve high-fat diet-induced endothelial dysfunction in mice conditionally lacking endothelial SIRT1. In addition, anti-miR-204 delivered systemically prevented high-fat diet-induced endothelial dysfunction and vascular SIRT1 decrease. Finally, serum from mice on antibiotics suppressed miR-204, and increased SIRT1, in endothelial cells, effects that were not observed with serum from mice in which antibiotics were discontinued. Therefore, the gut flora remotely downregulates endothelial SIRT1 through miR-204, leading to impairment of endothelial function.
Details
- Title: Subtitle
- Abstract 14050: The Gut Flora Promotes Endothelial Dysfunction Through Vascular MicroRNA-204-mediated Down-regulation of Endothelial Sirtuin1
- Creators
- Ajit Vikram - University of IowaYoung-Rae Kim - University of IowaSantosh Kumar - University of IowaJulia S Jacobs - University of IowaKaikobad Irani - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.130(suppl_2)
- DOI
- 10.1161/circ.130.suppl_2.14050
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/25/2014
- Academic Unit
- Radiation Oncology; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984315660002771
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