Acetylsalicylic acid inhibits monocyte adhesion to endothelial cells by an antioxidative mechanism.
The adhesion of monocytes to vascular endothelium increases in the presence of high levels of low density lipoprotein (LDL). LDL changes oxidative status of endothelial cells leading to an increased expression of cell adhesion molecules. Acetylsalicylic acid (ASA) has been shown to exert antioxidant effects in high and very high concentrations. This study was designed to demonstrate the influence of acetylsalicylic acid and its major metabolite, salicylic acid (SA), on the adhesion of monocytes to LDL-stimulated endothelial cells. Monocyte adhesion to endothelial cells was concentration-dependently inhibited by both salicylates upon stimulation of endothelial cells with TNF-alpha, oxidized LDL (oxLDL), and native LDL (nLDL). The inhibitory effect of ASA was more potent than that of SA, whereas the cyclooxygenase inhibitor ibuprofen had no effect. F2-isoprostane release from LDL-stimulated endothelial cells was reduced by simultaneous incubation with ASA or SA, whereas ibuprofen had no effect. LDL-induced activation of the transcription factor NF-kappaB was inhibited by ASA, and ferritin protein was increased when endothelial cells were incubated with this drug. These results show that acetylsalicylic acid and-less potently-salicylic acid inhibit monocyte adhesion to LDL-stimulated endothelial cells by antioxidative effects. For ASA, the observed inhibition of monocyte adhesion was accomplished with concentrations that can be reached after single oral doses of 500 mg of ASA.
Eisele
Guido
G
Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology, University Hospital Hamburg-Eppendorf, Germany.
Schwedhelm
Edzard
E
Schieffer
Bernhard
B
Tsikas
Dimitrios
D
Böger
Rainer H
RH
D000975:Antioxidants / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D001241:Aspirin