Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves

Ricardo A. Peña-Silva, Jordan D. Miller, Yi Chu, Donald D. Heistad

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Heart valve disease and pulmonary hypertension, in patients with carcinoid tumors and people who used the fenfluramine-phentermine combination for weight control, have been associated with high levels of serotonin in blood. The mechanism by which serotonin induces valvular changes is not well understood. We recently reported that increased oxidative stress is associated with valvular changes in aortic valve stenosis in humans and mice. In this study, we tested the hypothesis that serotonin induces oxidative stress in human heart valves, and examined mechanisms by which serotonin may increase reactive oxygen species. Superoxide (O2.-) was measured in heart valves from explanted human hearts that were not used for transplantation. O 2.- levels (lucigenin-enhanced chemoluminescence) were increased in homogenates of cardiac valves and blood vessels after incubation with serotonin. A nonspecific inhibitor of flavin-oxidases (diphenyliodonium), or inhibitors of monoamine oxidase [MAO (tranylcypromine and clorgyline)], prevented the serotonin-induced increase in O2.-. Dopamine, another MAO substrate that is increased in patients with carcinoid syndrome, also increased O2.- levels in heart valves, and this effect was attenuated by clorgyline. Apocynin [an inhibitor of NAD(P)H oxidase] did not prevent increases in O2.- during serotonin treatment. Addition of serotonin to recombinant human MAO-A generated O2.-, and this effect was prevented by an MAO inhibitor. In conclusion, we have identified a novel mechanism whereby MAO-A can contribute to increased oxidative stress in human heart valves and pulmonary artery exposed to serotonin and dopamine.

Original languageEnglish (US)
Pages (from-to)H1354-H1360
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number4
DOIs
StatePublished - Oct 2009

Keywords

  • Carcinoid syndrome
  • Reactive oxygen species
  • Serotonin
  • Superoxide
  • Valvulopathy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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