title: Static and cyclic tensile strain induce myxomatous effector proteins and serotonin in canine mitral valves.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Sciences, Colorado State University, 1678 Campus Delivery, Fort Collins, CO 80523-1678, USA. Carla.Lacerda@colostate.edu
authors.forename: Carla M R
authors.initials: CM
authors.lastname: Lacerda
authors.forename: Holly B
authors.initials: HB
authors.lastname: Maclea
authors.forename: John D
authors.initials: JD
authors.lastname: Kisiday
authors.forename: E Christopher
authors.initials: EC
authors.lastname: Orton
mesh_terms: D000818:Animals; D015415:Biomarkers; D001696:Biomechanical Phenomena; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005786:Gene Expression Regulation / Q000502:physiology*; D015151:Immunoblotting; D008943:Mitral Valve / Q000378:metabolism* / Q000473:pathology; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D012701:Serotonin