title: Emerging pathogenic mechanisms in human myxomatous mitral valve: lessons from past and novel data.
abstract: BACKGROUND
  Myxomatous mitral valve is one of the most common heart valves diseases in human and has been well characterized at a functional and morphological level. Diseased valves are thickened as a result of extracellular matrix remodeling and proteoglycans accumulation accompanied by the disruption of the stratified structures of the leaflets.
  
  
  METHODS
  Global transcriptomic analysis was used as a start-up to investigate potential pathogenic mechanisms involved in the development of the human idiopathic myxomatous mitral valve, which have been elusive for many years.
  
  
  RESULTS
  These prospective analyses have highlighted the potential role of apparently unrelated molecules in myxomatous mitral valve such as members of the transforming growth factor-β superfamily, aggrecanases of the "a disintegrin and metalloprotease with thrombospondin repeats I" family, and a weakening of the protection against oxidative stress. We have integrated, in this review, recent transcriptomic data from our laboratory [A. Hulin, C.F. Deroanne, C.A. Lambert, B. Dumont, V. Castronovo, J.O. Defraigne, et al. Metallothionein-dependent up-regulation of TGF-beta2 participates in the remodelling of the myxomatous mitral valve. Cardiovasc Res 2012;93:480-489] and from the publication of Sainger et al. [R. Sainger, J.B. Grau, E. Branchetti, P. Poggio, W.F. Seefried, B.C. Field, et al. Human myxomatous mitral valve prolapse: role of bone morphogenetic protein 4 in valvular interstitial cell activation. J Cell Physiol 2012;227:2595-2604] with existing literature and information issued from the study of monogenic syndromes and animal models.
  
  
  CONCLUSIONS
  Understanding cellular alterations and molecular mechanisms involved in myxomatous mitral valve should help at identifying relevant targets for future effective pharmacological therapy to prevent or reduce its progression.
authors.affiliation: Laboratory of Connective Tissues Biology, GIGA, University of Liège, Liège, Belgium.
authors.forename: Alexia
authors.initials: A
authors.lastname: Hulin
authors.forename: Christophe
authors.initials: C
authors.lastname: Deroanne
authors.forename: Charles
authors.initials: C
authors.lastname: Lambert
authors.forename: Jean-Olivier
authors.initials: JO
authors.lastname: Defraigne
authors.forename: Betty
authors.initials: B
authors.lastname: Nusgens
authors.forename: Marc
authors.initials: M
authors.lastname: Radermecker
authors.forename: Alain
authors.initials: A
authors.lastname: Colige
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D008943:Mitral Valve / Q000378:metabolism / Q000473:pathology*; D008945:Mitral Valve Prolapse / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D010641:Phenotype; D011379:Prognosis; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D055411:TGF-beta Superfamily Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D011509:Proteoglycans; D055411:TGF-beta Superfamily Proteins; D012701:Serotonin; D051722:ADAM Proteins