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Statins Block the Formation of Lipid Raft Redox Signaling Platforms in Coronary Endothelial Cells
Author(s) -
Hu JunJun,
Jia SuJie,
Li PinLan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.937.3
Subject(s) - lipid raft , nadph oxidase , chemistry , superoxide , microbiology and biotechnology , signal transduction , lovastatin , endothelial stem cell , fas ligand , endothelium , simvastatin , pharmacology , apoptosis , biochemistry , medicine , programmed cell death , biology , oxidative stress , cholesterol , enzyme , in vitro
Recent studies have reported that lipid raft (LR) redox signaling platforms associated with NADPH oxidase are involved in coronary endothelial dysfunction upon different injury factors. The present study was designed to test whether statins could interfere with the formation of LR redox signaling platforms to protect the coronary arterial endothelium from injury. By confocal microscopy, we first detected the formation of LRs clustering in human coronary arterial endothelial cells (HCAECs) exposed to FasL, a death receptor ligand. In these LR clusters, NADPH oxidase subunits, gp91 phox and p47 phox were aggregated with LR, which was almost completely blocked by statins (lovastatin, provastatin and simvastatin). To further explore the functional relevance of this action, we performed detergent resistant membrane floatation to isolate LRs. Electron spin resonance spectrometry showed that superoxide (O 2 .− ) production was 5‐fold higher in the LR fractions from FasL‐treated HCAECs than that from untreated cells. This FasL‐induced enhancement of O 2 .− production in LR fractions was substantially blocked by pretreatment with statins. Our results indicate that blockade of LR redox signaling platform formation in endothelial cell membrane may be another important therapeutic mechanism of statins in preventing endothelial injury and atherosclerosis.(Supported by NIH grants HL057244, HL075316, and DK054927)