Details

Autor(en) / Beteiligte

• Kruithof, Boudewijn P
• Van Wijngaarden, Aniek L
• Paardekooper, Laura
• Hiemstra, Yasmine L
• Goumans, Marie-José
• Palmen, Meindert
• Delgado, Victoria
• Ajmone Marsan, Nina

Titel

Abstract 13344: Stress-Induced Remodeling of the Mitral Valve: A Model for Superimposed Tissue Formation in Mitral Valve Prolapse

Ist Teil von

• Circulation (New York, N.Y.), 2019-11, Vol.140 (Suppl_1 Suppl 1), p.A13344-A13344

Ort / Verlag

by the American College of Cardiology Foundation and the American Heart Association, Inc

Erscheinungsjahr

2019

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• BackgroundIn mitral valve prolapse (MVP) leaflet thickening has recently been suggested to be due, in addition to myxomatous degeneration, to the presence of superimposed tissue (SIT), defined as an additional fibrous layer on top of the original leaflet. The mechanisms of SIT formation are currently unknown. We hypothesized that SIT formation would result from excessive leaflet stress.Purpose1) to assess the presence of SIT in resected mitral valve (MV) tissue from MVP patients undergoing surgery 2) to assess the correlation between leaflet remodeling and mechanical stress, using a unique ex-vivo model 3) to understand cellular and molecular mechanisms of SIT formation.MethodsHuman MVs (n=21) were histologically analyzed. Mouse MVs (n=26) were cultured in their natural position in the heart and subjected to various hemodynamic conditions representing specific phases of the cardiac cycle (closed and open MV) and the MVP configuration (Figure A).ResultsIn human MV, SIT was systematically observed, reaching up to 50% of total leaflet thickness and showed various compositions of extracellular matrix (Figure C). SIT formation was induced in the ex-vivo model, with similar characteristics as in human samples and clearly dependent on the duration, type and extent of mechanical stress (Figure E, B, F). Specific stainings and lineage tracing experiments showed that SIT comprises of macrophages and myofibroblasts and is associated with the activation of the transforming growth factor-beta and bone morphogenetic protein signaling pathways. Migration of valvular interstitial cells and macrophages through breakages of the endothelial cell lining contributed to SIT formation.ConclusionsMechanical stresses induce specific cellular and molecular changes in the MV that result in SIT formation. These observations provide the first insights in the mechanism of SIT formation and represent an initial step to identify potential novel and early treatment for MVP.