title: Mitral valve leaflet remodelling during pregnancy: insights into cell-mediated recovery of tissue homeostasis.
abstract: Little is known about how valvular tissues grow and remodel in response to altered loading. In this work, we used the pregnancy state to represent a non-pathological cardiac volume overload that distends the mitral valve (MV), using both extant and new experimental data and a modified form of our MV structural constitutive model. We determined that there was an initial period of permanent set-like deformation where no remodelling occurs, followed by a remodelling phase that resulted in near-complete restoration of homeostatic tissue-level behaviour. In addition, we observed that changes in the underlying MV interstitial cell (MVIC) geometry closely paralleled the tissue-level remodelling events, undergoing an initial passive perturbation followed by a gradual recovery to the pre-pregnant state. Collectively, these results suggest that valvular remodelling is actively mediated by average MVIC deformations (i.e. not cycle to cycle, but over a period of weeks). Moreover, tissue-level remodelling is likely to be accomplished by serial and parallel additions of fibrillar material to restore the mean homeostatic fibre stress and MVIC geometries. This finding has significant implications in efforts to understand and predict MV growth and remodelling following such events as myocardial infarction and surgical repair, which also place the valve under altered loading conditions.
authors.affiliation: Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences, Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712-0027, USA.
authors.forename: Bruno V
authors.identifier: 0000-0002-6315-693X
authors.initials: BV
authors.lastname: Rego
authors.affiliation: School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Wells
authors.affiliation: Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences, Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712-0027, USA.|School of Aerospace and Mechanical Engineering, The University of Oklahoma, Norman, OK 73019-1052, USA.
authors.forename: Chung-Hao
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences, Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712-0027, USA msacks@ices.utexas.edu.
authors.forename: Michael S
authors.identifier: 0000-0002-2711-8370
authors.initials: MS
authors.lastname: Sacks
mesh_terms: D000818:Animals; D002417:Cattle; D005260:Female; D008943:Mitral Valve / Q000502:physiology*; D011247:Pregnancy / Q000502:physiology*
keywords: heart valve; pregnancy; remodelling; structural constitutive model; valve interstitial cell; volume overload