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Title: On the role of predicted in vivo mitral valve interstitial cell deformation on its biosynthetic behavior. Author: Ayoub S, Howsmon DP, Lee CH, Sacks MS. Journal: Biomech Model Mechanobiol; 2021 Feb; 20(1):135-144. PubMed ID: 32761471. Abstract: Ischemic mitral regurgitation (IMR), a frequent complication of myocardial infarction, is characterized by regurgitation of blood from the left ventricle back into the left atrium. Physical interventions via surgery or less-invasive techniques are the only available therapies for IMR, with valve repair via undersized ring annuloplasty (URA) generally preferred over valve replacement. However, recurrence of IMR after URA occurs frequently and is attributed to continued remodeling of the MV and infarct region of the left ventricle. The mitral valve interstitial cells (MVICs) that maintain the tissue integrity of the MV leaflets are highly mechanosensitive, and altered loading post-URA is thought to lead to aberrant MVIC-directed tissue remodeling. Although studies have investigated aspects of mechanically directed VIC activation and remodeling potential, there remains a substantial disconnect between organ-level biomechanics and cell-level phenomena. Herein, we utilized an extant multiscale computational model of the MV that linked MVIC to organ-level MV biomechanical behaviors to simulate changes in MVIC deformation following URA. A planar biaxial bioreactor system was then used to cyclically stretch explanted MV leaflet tissue, emulating the in vivo changes in loading following URA. This simulation-directed experimental investigation revealed that post-URA deformations resulted in decreased MVIC activation and collagen mass fraction. These results are consistent with the hypothesis that URA failures post-IMR are due, in part, to reduced MVIC-mediated maintenance of the MV leaflet tissue resulting from a reduction in physical stimuli required for leaflet tissue homeostasis. Such information can inform the development of novel URA strategies with improved durability.[Abstract] [Full Text] [Related] [New Search]