MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery.
MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery.
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DOI：
10.1152/ajpheart.00574.2014
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Santhanam, Lakshmi
中科院分区：
文献类型：
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作者：
Kuo, Maggie M;Kim, Dae Hee;Santhanam, Lakshmi
硫化氢（H2S）已成为脉管系统中重要的气体递质。在这项研究中，我们验证了H2S有助于冠状动脉血管调节的假设，并评估了两种H2S来源的生理相关性，即半胱甘氨酸- γ -裂解酶（CSE）和3-巯基丙酮酸硫转移酶（MPST）。在人冠状动脉内皮细胞和大鼠、小鼠冠状动脉中检测到MPST；冠状血管未检出CSE。大鼠冠状动脉匀浆通过MPST途径产生H2S，而不是通过CSE途径产生H2S。在体内，CSE敲除小鼠、野生型小鼠（WT）和使用CSE抑制剂丙基甘氨酸处理的WT小鼠的冠状动脉血管松弛反应相似，这表明CSE产生的H2S在体内对冠状动脉血管调节没有显著作用。在体外，MPST底物3-巯基丙酮酸（3-MP）和H2S供体氢硫化钠（NaHS）引起了类似的冠状动脉反应性反应。丙酮酸对血管反应性没有任何影响。H2S的血管活性作用似乎依赖于一氧化氮（NO）： H2S诱导一氧化氮存在时冠状动脉血管收缩，一氧化氮不存在时血管松弛。3-MP和NaHS诱导收缩前张力增加后，最大内皮依赖性松弛未受影响，表明内皮NO合成酶活性未受到明显抑制。在体外，H2S与NO反应，这可能部分解释了3-MP和NaHS的血管收缩作用。综上所述，这些数据表明MPST而不是CSE在冠状动脉中产生H2S，通过直接调节NO介导其作用。这对健康和病变冠状动脉的h2s治疗具有重要意义。
Hydrogen sulfide (H2S) has emerged as an important gasotransmitter in the vasculature. In this study, we tested the hypothesis that H2S contributes to coronary vasoregulation and evaluated the physiological relevance of two sources of H2S, namely, cystathionine-gamma-lyase (CSE) and 3-mercaptypyruvate sulfertransferase (MPST). MPST was detected in human coronary artery endothelial cells as well as rat and mouse coronary artery; CSE was not detected in the coronary vasculature. Rat coronary artery homogenates produced H2S through the MPST pathway but not the CSE pathway in vitro. In vivo coronary vasorelaxation response was similar in CSE knockout mice, wild-type mice (WT), and WT mice treated with the CSE inhibitor propargylglycine, suggesting that CSE-produced H2S does not have a significant role in coronary vasoregulation in vivo. Ex vivo, the MPST substrate 3-mercaptopyruvate (3-MP) and H2S donor sodium hydrosulfide (NaHS) elicited similar coronary vasoreactivity responses. Pyruvate did not have any effects on vasoreactivity. The vasoactive effect of H2S appeared to be nitric oxide (NO) dependent: H2S induced coronary vasoconstriction in the presence of NO and vasorelaxation in its absence. Maximal endothelial-dependent relaxation was intact after 3-MP and NaHS induced an increase in preconstriction tone, suggesting that endothelial NO synthase activity was not significantly inhibited. In vitro, H2S reacted with NO, which may, in part explain the vasoconstrictive effects of 3-MP and NaHS. Taken together, these data show that MPST rather than CSE generates H2S in coronary artery, mediating its effects through direct modulation of NO. This has important implications for H2S-based therapy in healthy and diseased coronary arteries.