Annals of Biomedical Engineering

, Volume 46, Issue 5, pp 670–683 | Cite as

Eliminating Regurgitation Reduces Fibrotic Remodeling of Functional Mitral Regurgitation Conditioned Valves

  • Patrick S. Connell
  • Dragoslava P. Vekilov
  • Christine M. Diaz
  • Seulgi E. Kim
  • K. Jane Grande-Allen
Article

Abstract

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.

Keywords

Functional mitral regurgitation Mitral valve repair Organ culture 

Abbreviations

MV

Mitral valve

FMR

Functional mitral regurgitation

PM

Papillary muscle

GAG

Glycosaminoglycan

LOX

Lysyl oxidase

MMP-1

Matrix metalloproteinase-1

RUFLS

Rice University flow loop system

VIC

Valve interstitial cell

ECM

Extracellular matrix

LVAD

Left ventricular assist device

Notes

Acknowledgements

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.

Supplementary material

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Copyright information

© Biomedical Engineering Society 2018

Authors and Affiliations

  1. 1.Department of BioengineeringRice UniversityHoustonUSA
  2. 2.Department of PediatricsTexas Children’s Hospital and Baylor College of MedicineHoustonUSA

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