Serotonin produces MAO dependent oxidative stress in human heart valves

Serotonin (5HT) from carcinoid tumors and drugs (fen‐phen interactions) may contribute to development of valvulopathies and pulmonary hypertension. We determined whether 5HT induces oxidative stress in human heart valves, and examined mechanisms that may produce ROS. Superoxide (O2•−) was measured in heart valves from explanted human hearts that were rejected for transplantation. Superoxide levels (lucigenin‐enhanced chemoluminescence) were increased in valves and pulmonary artery after incubation with 5HT. Inhibitors of 5HT1 (GR55562) and 5HT2 receptors (ketanserin), and a selective serotonin reuptake blocker (fluoxetine) surprisingly did not prevent increases in superoxide. DPI (non‐specific inhibitor of flavin‐containing enzymes), tranylcypromine and clorgiline (inhibitors of MAO) abolished the increase in O2•−. Apocynin (inhibitor of NAD(P)H oxidase) and catalase did not prevent increase in O2•−. Addition of 5HT to human recombinant purified MAO‐A generated superoxide, and this effect was inhibited by a MAO inhibitor.

类癌肿瘤产生的5 - 羟色胺（5HT）以及药物（芬 - 芬相互作用）可能促使心脏瓣膜病和肺动脉高压的发生。我们确定了5HT是否会诱导人心脏瓣膜的氧化应激，并研究了可能产生活性氧（ROS）的机制。对因移植被拒的移植供体心脏的心脏瓣膜中的超氧化物（O₂•⁻）进行了检测。在与5HT孵育后，心脏瓣膜和肺动脉中的超氧化物水平（光泽精增强化学发光法测定）升高。5HT₁受体抑制剂（GR55562）和5HT₂受体抑制剂（酮色林）以及一种选择性5 - 羟色胺再摄取阻滞剂（氟西汀）令人惊讶地未能阻止超氧化物的增加。二亚苯基碘鎓（DPI，含黄素酶的非特异性抑制剂）、反苯环丙胺和氯吉兰（单胺氧化酶抑制剂）消除了O₂•⁻的增加。夹竹桃麻素（NAD（P）H氧化酶抑制剂）和过氧化氢酶未能阻止O₂•⁻的增加。向人重组纯化的单胺氧化酶A中添加5HT会产生超氧化物，且这种作用可被一种单胺氧化酶抑制剂抑制。