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Serotonin produces MAO dependent oxidative stress in human heart valves
Author(s) -
Silva Ricardo Alfonso Pena,
Miller Jordan D,
Heistad Donald D
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.747.6
Subject(s) - lucigenin , apocynin , superoxide , ketanserin , chemistry , pharmacology , 5 ht receptor , serotonin , oxidative stress , nox1 , oxidase test , catalase , medicine , endocrinology , receptor , biochemistry , enzyme
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 (O 2 •− ) 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 O 2 •− . Apocynin (inhibitor of NAD(P)H oxidase) and catalase did not prevent increase in O 2 •− . Addition of 5HT to human recombinant purified MAO‐A generated superoxide, and this effect was inhibited by a MAO inhibitor. Conclusion: Superoxide is increased in human vessels and heart valves exposed to high levels of 5HT by a mechanism that is independent of 5HT receptors. MAO is functional in the heart valves and mediates the increase in O 2 •− induced by serotonin.