Division of Pulmonary Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.
Mol Cells. 2012 Nov;34(5):449-55. doi: 10.1007/s10059-012-0200-5. Epub 2012 Oct 30.
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.
H2S 是一种与血管疾病（包括动脉粥样硬化）保护相关的信号分子。这种保护涉及血管舒张的刺激，但其他可能的贡献机制尚未得到广泛探索。在这项研究中，我们发现血管中 H2S 产生酶胱硫醚-γ-裂解酶（CSE）在各种血管调节剂中受到振荡剪切力（OSS）的下调。一致地，H2S 供体 NaHS 似乎抑制 OSS 诱导的 THP-1 细胞黏附。我们还发现，NaHS 激活了 Akt/内皮型一氧化氮合酶（eNOS）信号通路，以响应 OSS，而 NaHS 对 IκB 没有影响，IκB 是调节促炎信号通路的众所周知的分子。此外，NaHS 增加了 OSS 依赖性的 eNOS 表达，并降低了细胞间黏附分子-1（ICAM-1）的表达。一氧化氮合酶抑制剂 NG-硝基-L-精氨酸甲酯（L-NAME）消除了 NaHS 对 OSS 诱导的内皮细胞 ICAM-1 表达和单核细胞黏附到内皮细胞的抑制作用。这些数据表明，CSE 的下调导致 H2S 水平降低是 OSS 相关动脉粥样硬化形成的关键因素，并进一步表明 H2S 产生的调节可能是预防心血管疾病的潜在靶点。
