| Autor: |
Samuel C. R. Sherratt, Peter Libby, Hazem Dawoud, Deepak L. Bhatt, R. Preston Mason |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 13, Iss 14 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2047-9980 |
| DOI: |
10.1161/JAHA.123.034076 |
| Popis: |
Background Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor availability. Loss of endothelial function and NO bioavailability are associated with inflammation, including leukocyte activation. Eicosapentaenoic acid (EPA) administered as icosapent ethyl reduced cardiovascular events in REDUCE‐IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial) in relation to on‐treatment EPA blood levels. The mechanisms of cardiovascular protection for EPA remain incompletely elucidated but likely involve direct effects on the endothelium. Methods and Results In this study, human ECs were treated with EPA and challenged with the cytokine IL‐6 (interleukin‐6). Proinflammatory responses in the ECs were confirmed by ELISA capture of sICAM‐1 (soluble intercellular adhesion molecule‐1) and TNF‐α (tumor necrosis factor‐α). Global protein expression was determined using liquid chromatography–mass spectrometry tandem mass tag. Release kinetics of NO and peroxynitrite were monitored using porphyrinic nanosensors. IL‐6 challenge induced proinflammatory responses from the ECs as evidenced by increased release of sICAM‐1 and TNF‐α, which correlated with a loss of NO bioavailability. ECs pretreated with EPA modulated expression of 327 proteins by >1‐fold (P |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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