Aspirin inhibits thrombin action on endothelial cells via up-regulation of aminopeptidase N/CD13 expression.

OBJECTIVE

We hypothesized that aspirin may exhibit its anti-atherosclerotic effects via mechanisms other than cyclooxygenase inhibition in platelets.

METHODS AND

RESULTS

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.

CONCLUSIONS

Aspirin may exert its anti-atherothrombotic effects in part via the inhibition of thrombin action by up-regulating APN/CD13 on endothelial cells.