Static and cyclic tensile strain induce myxomatous effector proteins and serotonin in canine mitral valves

Carla M.R. Lacerda, Holly B. MacLea, John D. Kisiday, E. Christopher Orton

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Objectives: Degenerative (myxomatous) mitral valve disease is an important cardiac disease in dogs and humans. The mechanisms that initiate and propagate myxomatous pathology in mitral valves are poorly understood. We investigated the hypothesis that tensile strain initiates expression of proteins that mediate myxomatous pathology. We also explored whether tensile strain could induce the serotonin synthetic enzyme tryptophan hydroxylase 1 (TPH1), serotonin synthesis, and markers of chondrogenesis. Animals: Mitral valves were obtained postmortem from dogs without apparent cardiovascular disease. Methods: Mitral valves were placed in culture and subjected to 30% static or cyclic tensile strain and compared to cultured mitral valves subjected to 0% strain for 72 h. Abundance of target effector proteins, TPH1, and chondrogenic marker proteins was determined by immunoblotting. Serotonin was measured in the conditioned media by ELISA. Results: Both static and cyclic strain increased (p < 0.05) expression of myxomatous effector proteins including markers of an activated myofibroblast phenotype, matrix catabolic and synthetic enzymes in canine mitral valves compared to unstrained control. Expression of TPH1 was increased in statically and cyclically strained mitral valves. Expression of chondrogenic markers was increased in statically strained mitral valves. Serotonin levels were higher (p < 0.05) in media of cyclically strained valves compared to unstrained valves after 72 h of culture. Conclusion: Static or cyclic tensile strain induces acute increases in the abundance of myxomatous effector proteins, TPH1, and markers of chondrogenesis in canine mitral valves. Canine mitral valves are capable of local serotonin synthesis, which may be influenced by strain.

Original languageEnglish
Pages (from-to)223-230
Number of pages8
JournalJournal of Veterinary Cardiology
Volume14
Issue number1
DOIs
StatePublished - Mar 2012

Keywords

  • Chondrogenesis
  • Mitral valve
  • Myxomatous
  • Serotonin
  • Tensile strain

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