Tryptophan hydroxylase 1 expression is increased in phenotype-altered canine and human degenerative myxomatous mitral valves

Sirilak Disatian, Carla Lacerda, E. Christopher Orton

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background and aim of the study: Serotonin is a known mediator of myxomatous pathology in heart valves. Tryptophan hydroxylase 1 (TPH1) is the limiting enzyme for peripheral serotonin synthesis, and its expression by valve interstitial cells (IC) could implicate an autocrine serotonin signaling mechanism in primary degenerative myxomatous mitral valve disease. Thus, the expression of TPH1 in canine and human myxomatous mitral valves was determined, and IC phenotypes expressing TPH1 identified. Methods: TPH1 expression was determined in canine and human myxomatous and normal mitral valves by immunoblot (IB) and immunofluorescence microscopy (IFM). Co-localization of TPH1 expression with markers of IC phenotype transformation, a-smooth muscle actin (a-SMA) and non-muscle embryonic myosin (SMemb) was determined using double-IFM. Results: TPH1 expression by IB was increased (p <0.05) by three- to five-fold in canine early-stage and late-stage myxomatous valves, and in human surgically excised myxomatous valves compared to canine and human normal control valves, respectively. The number of TPH1 immunopositive cells per x400 field was increased (p <0.005) in canine (14.9 ± 1.2) and human (14.9 ± 2.9) myxomatous valves compared to canine (5.0 ± 2.4) and human (2.9 ± 0.6) normal control valves, respectively. Patterns for α-SMA and SMemb IC phenotype transformation were distinctly different in myxomatous valves. TPH1 expression was more closely associated with the SMemb IC phenotype in canine and human myxomatous valves. Conclusion: An increased expression of TPH1 in canine and human myxomatous mitral valves implicates an autocrine serotonin signaling mechanism in primary degenerative myxomatous mitral valves. TPH1 expression is associated with the SMemb-positive IC phenotype.

Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalJournal of Heart Valve Disease
Volume19
Issue number1
StatePublished - Jan 2010

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