Eliminating Regurgitation Reduces Fibrotic Remodeling of Functional Mitral Regurgitation Conditioned Valves
Functional mitral regurgitation (FMR) is an insidious and poorly understood condition affecting patients with myocardial disease. While current treatments reduce regurgitation, their ability to reverse mitral valve pathology is unclear. We utilized a pseudo-physiological flow loop to study how repair impacted valve composition. Porcine mitral valves were cultured in control geometry (native papillary muscle position and annular area) or high-tension FMR geometry (5 mm apical and 5 mm lateral displacement of papillary muscles, 65% increased annular area) for 2 weeks. To mimic repair, a reversal condition was created by returning one-week FMR conditioned valves to a non-regurgitant geometry and culturing for 1 week. Valve composition and material properties were analyzed. After two-week culture, FMR conditioned tissues were stiffer and stronger than control and underwent extensive fibrotic remodeling, with increased prolyl-4-hydroxylase, lysyl oxidase, matrix metalloproteinase-1, and decorin. The reversal condition displayed a heterogeneous, leaflet- and orientation-dependent response. Reversal-conditioned anterior leaflets and circumferential tissue sections continued to have significant fibrotic remodeling compared to control, whereas reversal-conditioned posterior leaflets, chordae tendineae, and radial tissue sections had significantly decreased remodeling compared to FMR-conditioned tissues. These findings suggest current repairs only partially reverse pathology, underscoring the need for innovation in the treatment of FMR.
KeywordsFunctional mitral regurgitation Mitral valve repair Organ culture
Functional mitral regurgitation
Rice University flow loop system
Valve interstitial cell
Left ventricular assist device
The authors would like to acknowledge Dr. Larry Fisher, NIH for his gift of decorin antibody used in this research.
Conflicts of interest
Dr. Connell reports personal fees from Polyvascular Corporation, outside the submitted work. Other authors have no disclosures.
This work was supported by the National Science Foundation Graduate Research Fellowship Program [1450681 to D.V.]; and an American Heart Association Predoctoral Fellowship [13PRE14110003 to P.C.].
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