Effects of the selective COX-2 inhibitors celecoxib and rofecoxib on human vascular cells
| Autor: | Christine Manderscheid, Sabine Grösch, Gerd Geisslinger, Helmut Schmidt, Corina Ehnert, Ellen Niederberger |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Programmed cell death
Gene Expression Apoptosis Cell Cycle Proteins Prostacyclin Inflammation Pharmacology Biochemistry Muscle Smooth Vascular Lactones medicine Humans Cyclooxygenase Inhibitors Sulfones Cells Cultured Rofecoxib Sulfonamides Cyclooxygenase 2 Inhibitors biology business.industry Cell Cycle Membrane Proteins Thromboxanes Cell cycle Epoprostenol Isoenzymes Endothelial stem cell Celecoxib Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Immunology biology.protein Pyrazoles Endothelium Vascular Cyclooxygenase medicine.symptom business Cell Division medicine.drug |
| Zdroj: | Biochemical Pharmacology. 68:341-350 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/j.bcp.2004.03.029 |
| Popis: | Rheumatoid arthritis (RA) is associated with a reduced life expectancy considered to be partly caused by cardiovascular events. A growing concern is that accelerated atherosclerosis is driven by inflammatory mechanisms similar to those responsible for RA. Therefore, selective COX-2 inhibitors, which are widely used for the symptomatic treatment of pain and inflammation in RA, may have an impact on atherosclerotic processes. Their anti-inflammatory properties might provoke anti-atherogenic effects but on the other hand, selective inhibition of anti-thrombotic prostacyclin and COX-2 independent effects might promote the risk of increased prothrombotic activity. In the current study, the effects of the presently marketed selective COX-2 inhibitors celecoxib and rofecoxib on vascular cells have been investigated. Celecoxib inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. At high concentrations, it induced apoptosis and the modulation of inhibitory cell cycle proteins. In contrast rofecoxib-even at high concentrations-had no effect on cell proliferation, apoptosis or cell cycle distribution indicating that celecoxib and rofecoxib do not affect the same signal transduction pathways in endothelial cells. Both drugs did not affect apoptosis induction or cell cycle proliferation in human vascular smooth muscle cells. The observed effects on endothelial cells appear to be COX-independent since both drugs selectively inhibited COX-2-activity and the applied concentrations lay beyond the IC(50) for inhibition of prostacyclin production. Regarding endothelial apoptosis as a relevant event in the initiation and progression of atherosclerosis the present data put forward the hypothesis that the presently marketed COX-2 inhibitors have a different impact on atherosclerotic processes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect