H2S is a signaling molecule associated with protection against vascular diseases, including atherosclerosis. This protection involves the stimulation of vasorelaxation, but other possible contributing mechanisms have not been extensively explored. In this study, we found that the vascular H2S-producing enzyme, cystathionine-?-lyase (CSE), was down-regulated by oscillatory shear stress (OSS) among various vaso-regulators. Consistently, NaHS, an H2S donor, appeared to inhibit OSS-induced THP-1 cell adhesion. We also found that NaHS activated the nitric oxide (NO)-producing Akt/endothelial nitric oxide synthase (eNOS) signaling pathway in response to OSS, whereas NaHS had no effect on I?B, a well-known molecule regulating pro-inflammatory signaling pathways. Moreover, NaHS increased OSS-dependent eNOS expression and decrea-sed expression of intercellular adhesion molecule-1 (ICAM-1). NG-nitro-L-arginine methyl ester (L-NAME), an eNOS inhibitor, abrogated the inhibitory effects of NaHS on OSS-induced endothelial ICAM-1 expression and monocyte adhesion to endothelial cells. These data sug-gest that down-regulation of CSE resulting in decreased levels of H2S is a key factor for OSS-associated athero-genesis and further suggest that regulation of H2S production can be a potential target for preventing cardiovascular diseases.

Keywords: cystathionine-?-lyase, endothelial nitric oxide synthase, H2S, ICAM-1, oscillatory shear stress