Abstract 17274: Increased Fibroblast Activation Protein and Matrix Metalloproteinase- 9 Expression are Associated With Altered Extra-Cellular Matrix Changes in Barlow’s Disease Compared to Fibro Elastic Deficiency in Mitral Valve Degenerative Disease - Implication in Disease Progression
Introduction: Surgically defined degenerative mitral valve disease (DMVD) - Barlow’s disease (BD) and Fibro elastic deficiency (FED) may differ histologically. This may impart structural and functional differences in the extracellular matrix (ECM) remodeling. However ECM remodeling was not well characterized in these entities. Recently, it has been reported that Fibroblast Activation Protein (FAP), a serine protease may play an essential role in ECM remodeling in association with matrix metalloproteinase-9 (MMP-9) expression.
Hypothesis: We hypothesize that altered FAP and MMP-9 protein expression may be linked to altered collagen deposition in BD compared to FED.
Methods: Twenty human posterior mitral valve leaflets (10 from BD and 10 from FED) were studied. FAP and MMP-9 protein expressions were graded by immunohistochemistry. Collagens composition was evaluated by Picro-sirius red and polarization microscopy, valvular interstitial cells (VICs) by immunochemistry and elastic fibrils by elastic trichrome stain.
Results: See figure and table. Decreased FAP (p= 0.0001) and increased MMP-9 protein expression (p=0.07) were seen in BD compared to FED. VICs and type III collagen deposition were decreased in BD when compared to FED, indicating FED as an active and progressive lesion when compared to BD. (p =NS).
Conclusions: Altered fibroblast activation protein and MMP-9 expression are associated with extracellular matrix changes in Barlow’s disease. These findings may contribute to disease progression in Barlow’s and FED, specifically related to pathological ECM remodeling. Molecular mediators using micro RNA (miRNA) are under investigation to further elucidate these pathways.
Author Disclosures: P. K-Raman: None. M. Purushothaman: None. D.H. Adams: None. P. Krishnan: None. A. Kini: None. S.K. Sharma: None. V. Fuster: None. P.R. Moreno: None.
- © 2014 by American Heart Association, Inc.