title: Load-dependent extracellular matrix organization in atrioventricular heart valves: differences and similarities.
abstract: The extracellular matrix of the atrioventricular (AV) valves' leaflets has a key role in the ability of these valves to properly remodel in response to constantly varying physiological loads. While the loading on mitral and tricuspid valves is significantly different, no information is available on how collagen fibers change their orientation in response to these loads. This study delineates the effect of physiological loading on AV valves' leaflets microstructures using Second Harmonic Generation (SHG) microscopy. Fresh natural porcine tricuspid and mitral valves' leaflets (n = 12/valve type) were cut and prepared for the experiments. Histology and immunohistochemistry were performed to compare the microstructural differences between the valves. The specimens were imaged live during the relaxed, loading, and unloading phases using SHG microscopy. The images were analyzed with Fourier decomposition to mathematically seek changes in collagen fiber orientation. Despite the similarities in both AV valves as seen in the histology and immunohistochemistry data, the microstructural arrangement, especially the collagen fiber distribution and orientation in the stress-free condition, were found to be different. Uniaxial loading was dependent on the arrangement of the fibers in their relaxed mode, which led the fibers to reorient in-line with the load throughout the depth of the mitral leaflet but only to reorient in-line with the load in deeper layers of the tricuspid leaflet. Biaxial loading arranged the fibers in between the two principal axes of the stresses independently from their relaxed states. Unlike previous findings, this study concludes that the AV valves' three-dimensional extracellular fiber arrangement is significantly different in their stress-free and uniaxially loaded states; however, fiber rearrangement in response to the biaxial loading remains similar.
authors.affiliation: The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, California; Department Biomedical Engineering, University of California, Irvine, Irvine, California; and.
authors.forename: S Hamed
authors.initials: SH
authors.lastname: Alavi
authors.affiliation: The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, California; Department Biomedical Engineering, University of California, Irvine, Irvine, California; and.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Division of Cardiothoracic Surgery, University of California, Irvine, Irvine, California.
authors.forename: Earl
authors.initials: E
authors.lastname: Steward
authors.affiliation: Division of Cardiothoracic Surgery, University of California, Irvine, Irvine, California.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Milliken
authors.affiliation: The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, California; Department Biomedical Engineering, University of California, Irvine, Irvine, California; and arashkh@uci.edu.
authors.forename: Arash
authors.initials: A
authors.lastname: Kheradvar
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D024022:Fibrillar Collagens / Q000378:metabolism* / Q000648:ultrastructure; D005583:Fourier Analysis; D006439:Hemodynamics; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D040542:Mechanotransduction, Cellular; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods; D008943:Mitral Valve / Q000378:metabolism* / Q000648:ultrastructure; D023421:Models, Animal; D013314:Stress, Mechanical; D013552:Swine; D013997:Time Factors; D014261:Tricuspid Valve / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D024022:Fibrillar Collagens
keywords: biaxial load; collagen fibers; mechanics; uniaxial load