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Carvedilol inhibits tumor necrosis factor-alpha-induced endothelial transcription factor activation, adhesion molecule expression, and adhesiveness to human mononuclear cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Chen, Jaw-Wen Lin, Feng-Yen Chen, Yung-Hsiang Wu, Tao-Cheng Chen, Yuh-Lien Lin, Shing-Jong |
| Copyright Year | 2004 |
| Abstract | OBJECTIVE We tested the hypothesis that carvedilol, a beta-adrenoceptor and alpha-adrenoceptor antagonist with potent antioxidant property, could inhibit tumor necrosis factor-alpha (TNF-alpha)-induced endothelial adhesiveness to human mononuclear cells (MNCs), an early sign of atherogenesis. METHODS AND RESULTS Circulating MNCs were isolated from the peripheral blood of healthy subjects. Compared with control condition, pretreatment of carvedilol (10 micromol/L for 18 hours) or probucol (5 micromol/L for 18 hours), but not propanolol, prazosin, or both propanolol and prazosin significantly decreased TNF-alpha-stimulated adhesiveness of cultured human aortic endothelial cells (HAECs) to MNCs. Carvedilol inhibited TNF-alpha-stimulated endothelial vascular cell adhesion molecule-1 (VCAM-1) and E-selectin (66.0+/-2.0% and 55.60+/-1.0% of control, P<0.05, respectively) expression, whereas probucol inhibited only VCAM-1 expression (79.0+/-5.0% of control, P<0.05). Propanolol, prazosin, or both did not alter the expression of adhesion molecules. Further, pretreatment with carvedilol significantly inhibited TNF-alpha-stimulated intracellular reactive oxygen species (ROS) production and the activation of redox sensitive nuclear factor kappa B and activator protein-1 transcription pathways. CONCLUSIONS Carvedilol reduced TNF-alpha-stimulated endothelial adhesiveness to human MNCs by inhibiting intracellular ROS production, transcription factor activation, and VCAM-1 as well as E-selectin expression, suggesting its potential role in clinical atherosclerosis disease. |
| File Format | PDF HTM / HTML |
| PubMed reference number | 15374848 |
| Journal | Medline |
| Volume Number | 24 |
| Issue Number | 11 |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/24/11/2075.full.pdf |
| Alternate Webpage(s) | http://homepage.ntu.edu.tw/~anatomy/teacher/Chen%20Yuh%20Lien/Bata_paper/30-Carvedilol%20Inhibits%20Tumor.pdf |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/24/11/2075.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1161/01.ATV.0000145016.69181.fa |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
