Journal article
CR6-Interacting Factor 1 Deficiency Impairs Vascular Function by Inhibiting the Sirt1-Endothelial Nitric Oxide Synthase Pathway
Antioxidants & redox signaling, Vol.27(4), pp.234-249
08/01/2017
DOI: 10.1089/ars.2016.6719
PMID: 28117598
Abstract
Aims: Mitochondrial dysfunction has emerged as a major contributing factor to endothelial dysfunction and vascular disease, but the key mechanisms underlying mitochondrial dysfunction-induced endothelial dysfunction remain to be elucidated. In this study, we aim at determining whether mitochondrial dysfunction in endothelial cells plays a key role in vascular disease, by examining the phenotype of endothelial-specific CR6-interacting factor 1 (CRIF1) knockout mice. We also used siRNA-mediated downregulation of CRIF1 gene in the endothelial cells to study about the in vitro pathophysiological underlying mechanisms.
Results: Downregulation of CRIF1 in endothelial cells caused disturbances of mitochondrial oxidative phosphorylation complexes and membrane potential, leading to enhanced mitochondrial reactive oxygen species production. Gene silencing of CRIF1 results in decreased SIRT1 expression along with increased endothelial nitric oxide synthase ( eNOS) acetylation, leading to reduced nitric oxide production both in vitro and in vivo. Endothelium-dependent vasorelaxation of aortic rings from CRIF1 knockout ( KO) mice was considerably less than in wild-type mice, and it was partially recovered by Sirt1 overexpression in CRIF1 KO mice.
Innovation: Our results show for the first time a relationship between mitochondrial dysfunction and impaired vascular function induced in CRIF1 deficiency conditions and also the possible underlying pathway involved.
Conclusion: These findings indicate that CRIF1 plays an important role in maintaining mitochondrial and endothelial function through its effects on the SIRT1-eNOS pathway.
Details
- Title: Subtitle
- CR6-Interacting Factor 1 Deficiency Impairs Vascular Function by Inhibiting the Sirt1-Endothelial Nitric Oxide Synthase Pathway
- Creators
- Harsha Nagar - Chungnam National UniversitySaet-byel Jung - Chungnam National UniversityMin Jeong Ryu - Chungnam National UniversitySu-Jung Choi - Chungnam National UniversityShuyu Piao - Chungnam National UniversityHee-Jung Song - Chungnam National University HospitalShin Kwang Kang - Chungnam National University HospitalNara Shin - Chungnam National UniversityDong Woon Kim - Chungnam National UniversitySeon-Ah Jin - Chungnam National UniversityJin-Ok Jeong - Chungnam National UniversityKaikobad Irani - Roy J. and Lucille A. Carver College of MedicineByeong Hwa Jeon - Chungnam National UniversityMinho Shong - Chungnam National UniversityGi Ryang Kweon - Chungnam National UniversityCuk-Seong Kim - Chungnam National University
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.27(4), pp.234-249
- Publisher
- Mary Ann Liebert, Inc
- DOI
- 10.1089/ars.2016.6719
- PMID
- 28117598
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Number of pages
- 16
- Grant note
- NRF-2014R1A6A1029617; NRF-2015R1D1A1A01061516 / National Research Foundation of Korea (NRF) - Ministry of Education
- Language
- English
- Date published
- 08/01/2017
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984313085602771
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