Journal article
Sirtuin1 protects endothelial Caveolin-1 expression and preserves endothelial function via suppressing miR-204 and endoplasmic reticulum stress
Scientific reports, Vol.7(1), pp.42265-42265
02/09/2017
DOI: 10.1038/srep42265
PMCID: PMC5299412
PMID: 28181559
Abstract
Sirtuin1 (Sirt1) is a class III histone deacetylase that regulates a variety of physiological processes, including endothelial function. Caveolin1 (Cav1) is also an important determinant of endothelial function. We asked if Sirt1 governs endothelial Cav1 and endothelial function by regulating miR-204 expression and endoplasmic reticulum (ER) stress. Knockdown of Sirt1 in endothelial cells, and in vivo deletion of endothelial Sirt1, induced endothelial ER stress and miR-204 expression, reduced Cav1, and impaired endothelium-dependent vasorelaxation. All of these effects were reversed by a miR-204 inhibitor (miR-204 I) or with overexpression of Cav1. A miR-204 mimic (miR-204 M) decreased Cav1 in endothelial cells. In addition, high-fat diet (HFD) feeding induced vascular miR-204 and reduced endothelial Cav1. MiR-204-I protected against HFD-induced downregulation of endothelial Cav1. Moreover, pharmacologic induction of ER stress with tunicamycin downregulated endothelial Cav1 and impaired endothelium-dependent vasorelaxation that was rescued by overexpressing Cav1. In conclusion, Sirt1 preserves Cav1-dependent endothelial function by mitigating miR-204-mediated vascular ER stress.
Details
- Title: Subtitle
- Sirtuin1 protects endothelial Caveolin-1 expression and preserves endothelial function via suppressing miR-204 and endoplasmic reticulum stress
- Creators
- Modar Kassan - Roy J. and Lucille A. Carver College of MedicineAjit Vikram - Roy J. and Lucille A. Carver College of MedicineYoung-Rae Kim - Roy J. and Lucille A. Carver College of MedicineQiuxia Li - Roy J. and Lucille A. Carver College of MedicineAdam Kassan - University of California SystemHemal H Patel - VA San Diego Healthcare SystemSantosh Kumar - Roy J. and Lucille A. Carver College of MedicineMohanad Gabani - Roy J. and Lucille A. Carver College of MedicineJing Liu - Roy J. and Lucille A. Carver College of MedicineJulia S Jacobs - Roy J. and Lucille A. Carver College of MedicineKaikobad Irani - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.7(1), pp.42265-42265
- DOI
- 10.1038/srep42265
- PMID
- 28181559
- PMCID
- PMC5299412
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Language
- English
- Date published
- 02/09/2017
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984313084902771
Metrics
20 Record Views