Journal article
The SCFFBXO3 ubiquitin E3 ligase regulates inflammation in atherosclerosis
Journal of molecular and cellular cardiology, Vol.126, pp.50-59
01/01/2019
DOI: 10.1016/j.yjmcc.2018.11.006
PMID: 30448480
Abstract
Inflammation is critical in the pathobiology of atherosclerosis. An essential player in the inflammatory process in atherosclerosis are macrophages that scavenge oxidatively modified low-density lipoproteins (OxLDL) deposited in the subendothelium of systemic arteries that secrete a myriad of pro-inflammatory mediators. Here, we identified that a subunit of the Skp-Cullin-F-box ubiquitin E3 ligase apparatus, termed FBXO3, modulates the inflammatory response in atherosclerosis. Specifically, individuals with a hypofunctioning genetic variant of FBXO3 develop less atherosclerosis. FBXO3 protein is present in cells of monocytic lineage within carotid plaques and its levels increase in those with symptomatic compared with asymptomatic atherosclerosis. Further, cellular depletion or small molecule inhibition of FBXO3 significantly reduced the inflammatory response to OxLDL by macrophages without altering OxLDL uptake. Thus, FBXO3 potentiates vascular inflammation and atherosclerosis that can be effectively mitigated by a small molecule inhibitor.
Details
- Title: Subtitle
- The SCFFBXO3 ubiquitin E3 ligase regulates inflammation in atherosclerosis
- Creators
- Divay Chandra - University of PittsburghJames Londino - University of PittsburghShaun Alexander - University of PittsburghJoseph S. Bednash - University of PittsburghYingze Zhang - University of PittsburghRobert M. Friedlander - University of PittsburghGrant Daskivich - University of PittsburghDiane L. Carlisle - University of PittsburghWilliam R. Lariviere - University of PittsburghAna Carolina Igami Nakassa - University of PittsburghMark Ross - University of PittsburghClaudette St. Croix - University of PittsburghToru Nyunoya - University of PittsburghFrank Sciurba - University of PittsburghBill Chen - University of PittsburghRama K. Mallampalli - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.126, pp.50-59
- DOI
- 10.1016/j.yjmcc.2018.11.006
- PMID
- 30448480
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Publisher
- Elsevier Ltd
- Number of pages
- 10
- Language
- English
- Date published
- 01/01/2019
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985214168402771
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