Biaxial stress relaxation of semilunar heart valve leaflets during simulated collagen catabolism: Effects of collagenase concentration and equibiaxial strain state

Huang, Siyao; Huang, Hsiao‐Ying Shadow

doi:10.1177/0954411915604336

Cited by 22 publications

(14 citation statements)

References 62 publications

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“…Furthermore, the group of Bodi showed that in swine, and more importantly in human, the collagen organization at the outer region of the myocardial infarcted area was more disorganized and random compared to the core region [11]. Other mechanical properties that changed during valvular ECM remodeling have been shown to affect VIC phenotypic change and functions, for example stress relaxation [12] and transvalvular pressure [13]. For this manuscript, we are specifically interested in the effect of randomized stiffness organization, which results from new deposited collagen fibers on VIC phenotypic change.…”

Section: Introductionmentioning

confidence: 99%

Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization

Killaars

DelRio

et al. 2017

Biomaterials

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Valvular interstitial cells (VICs) are key regulators of the heart valve’s extracellular matrix (ECM), and upon tissue damage, quiescent VIC fibroblasts become activated to myofibroblasts. As the behavior of VICs during disease progression and wound healing is different compared to healthy tissue, we hypothesized that the organization of the matrix mechanics, which results from depositing of collagen fibers, would affect VIC phenotypic transition. Specifically, we investigated how the subcellular organization of ECM mechanical properties affects subcellular localization of Yes-associated protein (YAP), an early marker of mechanotransduction, and α-smooth muscle actin (α-SMA), a myofibroblast marker, in VICs. Photo-tunable hydrogels were used to generate substrates with different moduli and to create organized and disorganized patterns of varying elastic moduli. When porcine VICs were cultured on these matrices, YAP and α-SMA activation were significantly increased on substrates with higher elastic modulus or a higher percentage of stiff regions. Moreover, VICs cultured on substrates with a spatially disorganized elasticity had smaller focal adhesions, less nuclear localized YAP, less α-SMA organization into stress fibers and higher proliferation compared to those cultured on substrates with a regular mechanical organization. Collectively, these results suggest that disorganized spatial variations in mechanics that appear during wound healing and fibrotic disease progression may influence the maintenance of the VIC fibroblast phenotype, causing more proliferation, ECM remodeling and matrix deposition.

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Section: Introductionmentioning

confidence: 99%

Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization

Killaars

DelRio

et al. 2017

Biomaterials

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“…Several types of collagen are thought to be protected from enzymatic breakdown under low and moderate forces, but are made vulnerable to degradation by higher forces, as large deformations expose sites of protease binding [25][26][27]. In a collagen network under high pre-stretch (e.g.…”

Section: Delayed Restoration Of Homeostasismentioning

confidence: 99%

Mitral valve leaflet remodelling during pregnancy: insights into cell-mediated recovery of tissue homeostasis

Rego

Wells

Lee

et al. 2016

J. R. Soc. Interface.

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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.

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“…It is worth noting that cells are not the only components that are sensitive to changes in mechanical loading [ 43 ]. While large mechanical strains could increase the rate of extracellular matrix catabolism in cardiac valves [ 44 ], studies have shown that the extracellular matrix collagen is more stable and degrades more slowly under homeostatic mechanical strain [ 45 – 47 ]. Considering such an important influence of the tissue mechanical milieu on short-term as well as long-term valve responses, it is essential to not ignore dilation in the annulus following chordae rupture.…”

Section: Discussionmentioning

confidence: 99%

Dilation of tricuspid valve annulus immediately after rupture of chordae tendineae in ex-vivo porcine hearts

Khoiy

Asgarian²,

Loth

et al. 2018

PLoS ONE

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PurposeChordae rupture is one of the main lesions observed in traumatic heart events that might lead to severe tricuspid valve (TV) regurgitation. TV regurgitation following chordae rupture is often well tolerated with few or no symptoms for most patients. However, early repair of the TV is of great importance, as it might prevent further exacerbation of the regurgitation due to remodeling responses. To understand how TV regurgitation develops following this acute event, we investigated the changes on TV geometry, mechanics, and function of ex-vivo porcine hearts following chordae rupture.MethodsSonomicrometry techniques were employed in an ex-vivo heart apparatus to identify how the annulus geometry alters throughout the cardiac cycle after chordae rupture, leading to the development of TV regurgitation.ResultsWe observed that the TV annulus significantly dilated (~9% in area) immediately after chordae rupture. The annulus area and circumference ranged from 11.4 ± 2.8 to 13.3 ± 2.9 cm2 and from 12.5 ± 1.5 to 13.5 ± 1.3 cm, respectively, during the cardiac cycle for the intact heart. After chordae rupture, the annulus area and circumference were larger and ranged from 12.3 ± 3.0 to 14.4 ± 2.9 cm2 and from 13.0 ± 1.5 to 14.0 ± 1.2 cm, respectively.ConclusionsIn our ex-vivo study, we showed for the first time that the TV annulus dilates immediately after chordae rupture. Consequently, secondary TV regurgitation may be developed because of such changes in the annulus geometry. In addition, the TV leaflet and the right ventricle myocardium are subjected to a different mechanical environment, potentially causing further negative remodeling responses and exacerbating the detrimental outcomes of chordae rupture.

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Biaxial stress relaxation of semilunar heart valve leaflets during simulated collagen catabolism: Effects of collagenase concentration and equibiaxial strain state

Cited by 22 publications

References 62 publications

Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization

Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization

Mitral valve leaflet remodelling during pregnancy: insights into cell-mediated recovery of tissue homeostasis

Dilation of tricuspid valve annulus immediately after rupture of chordae tendineae in ex-vivo porcine hearts

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