H(2)S inhibits oscillatory shear stress-induced monocyte binding to endothelial cells via nitric oxide production.

H(2)S 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 H(2)S-producing enzyme, cystathionine-γ-lyase (CSE), was down-regulated by oscillatory shear stress (OSS) among various vaso-regulators. Consistently, NaHS, an H(2)S 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 IκB, a well-known molecule regulating pro-inflammatory signaling pathways. Moreover, NaHS increased OSS-dependent eNOS expression and decreased 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 OSSinduced endothelial ICAM-1 expression and monocyte adhesion to endothelial cells. These data suggest that down-regulation of CSE resulting in decreased levels of H(2)S is a key factor for OSS-associated atherogenesis and further suggest that regulation of H(2)S production can be a potential target for preventing cardiovascular diseases.