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Reciprocal interactions between mitral valvular endothelial and interstitial cells regulate endothelial‐to‐mesenchymal transformation and myofibroblast activation
Author(s) -
Shapero Kayle,
Bischoff Joyce,
Mayer John
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.530.3
Subject(s) - myofibroblast , mesenchymal stem cell , mitral valve , microbiology and biotechnology , phenotype , cardiac valve , endothelium , biology , fibrosis , medicine , gene , genetics
Mitral valve pathologies are characterized by thickening of the valve leaflets, activated myofibroblasts, and excessive matrix remodeling. The mechanisms leading to these alterations are not well‐understood due to a lack of understanding of valve endothelial cells (VEC) and valve interstitial cells (VIC), and how the two cells interact to maintain valve structure and function. Hypothesis We propose that VEC‐VIC interactions are required for normal growth, integrity and function of valves. Results We characterized mitral VEC and VIC populations isolated from ovine mitral valves. We modeled VEC‐VIC interactions in vitro using indirect co‐culture in Transwells. In these assays, VICs suppressed TGFβ‐mediated endothelial‐to‐mesenchymal transformation (EndMT) in the VECs. Conversely, co‐culture of VECs and VICs suppressed the activated myofibroblast phenotype in VICs. Conclusions These results suggest that interactions between VEC and VIC are important for 1) suppressing EndMT in VECs and 2) suppressing the activated VIC phenotype. Healthy adult mitral valves exhibit little to no EndMT or activated VICs, two cellular processes implicated in valve disease. We speculate that disturbance of reciprocal interactions between VEC and VICs in vivo may contribute to pathologies characteristic of cardiac valves. Supported by internal funding and the Leducq Foundation Mitral Valve Network Grant.