Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723959.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity
Authors:Masuda, M.; Miyazaki-Anzai, S.; Keenan, A. L.; Okamura, K.; Kendrick, J.; Chonchol, M.; Offermanns, S.; Ntambi, J. M.; Kuro, O. M.; Miyazaki, M.
Date of Publication (YYYY-MM-DD):2015-12
Title of Journal:J Clin Invest
Volume:125
Issue / Number:12
Start Page:4544
End Page:4558
Audience:Not Specified
Abstract / Description:Recent evidence indicates that saturated fatty acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unsaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully saturated phosphatidic acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification.
Free Keywords:Animals; Endoplasmic Reticulum Stress/*drug effects/genetics; Mice; Mice, Knockout; Phosphatidylethanolamines/*toxicity; Stearoyl-CoA Desaturase/genetics/*metabolism; Vascular Calcification/chemically induced/genetics/*metabolism/pathology
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1558-8238 (Electronic) 0021-9738 (Linking) %R 10.1172/JCI82871
URL:http://www.ncbi.nlm.nih.gov/pubmed/26517697
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.