endothelin-1 and ubenimex

We hypothesized that aspirin may exhibit its anti-atherosclerotic effects via mechanisms other than cyclooxygenase inhibition in platelets.. Using enhanced subtraction hybridization analysis, we found in human umbilical vein endothelial cells (HUVECs) that aspirin up-regulates the expression of aminopeptidase N (APN/CD13) mRNA and its surface protein levels in a dose-dependent manner. Enzymatic activity of APN/CD13 on HUVECs was increased approximately 1.5-fold by 1 mmol L(-1) of aspirin, and treatment with bestatin, an inhibitor for APN/CD13 metalloprotease activity, attenuated the enhanced activities of APN/CD13. Since activated thrombin receptor is reported to be inactivated by APN/CD13 in vitro, protective actions of aspirin on HUVECs by thrombin stimulation were examined, resulting in the suppression of endothelin-1 and reactive oxygen species productions in HUVECs. These inhibitory actions of aspirin were partially abrogated by bestatin.. Aspirin may exert its anti-atherothrombotic effects in part via the inhibition of thrombin action by up-regulating APN/CD13 on endothelial cells.

Topics: Aspirin; CD13 Antigens; Cells, Cultured; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Enzyme Induction; Fibrinolytic Agents; Genes, Reporter; Humans; Leucine; Protease Inhibitors; Reactive Oxygen Species; RNA, Messenger; Subtraction Technique; Thrombin; Transcription, Genetic; Transfection; Umbilical Veins