The effects of cellular contraction on aortic valve leaflet flexural stiffness

The effects of cellular contraction on aortic valve leaflet flexural stiffness
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DOI:
10.1016/j.jbiomech.2004.11.008
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发表时间:
2006-01-01
影响因子:
2.4
通讯作者:
Sacks, MS
Sacks, MS
中科院分区:
工程技术3区
文献类型:
--
作者:
Merryman, WD;Huang, HYS;Sacks, MS

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主动脉瓣(AV)瓣叶包含一个异质性的间质细胞群,主要由肌成纤维细胞组成,其具有成纤维细胞和平滑肌细胞的双重特性。本研究的重点是检测完整瓣叶组织内主动脉瓣间质细胞(AVIC)的收缩行为。在弯曲条件下对猪主动脉瓣瓣叶的环形条带进行力学测试,使AVIC分别处于正常、收缩和收缩抑制状态。在添加90 mM KCl以诱导细胞收缩之前和之后,瓣叶分别顺着(WC)和逆着(AC)其自然瓣叶曲率弯曲。此外,通过用10 μM毒胡萝卜素处理瓣叶以完全抑制AVIC收缩,也证实了存在一种自然的基础张力。结果显示,当沿AC方向弯曲时,随着AVIC收缩,瓣叶刚度增加了48%(分别从703 kPa增加到1040 kPa)(p = 0.004),而在WC方向,活动状态下瓣叶刚度仅增加5%(分别从491 kPa增加到516.5 kPa,无显著差异)。此外,用毒胡萝卜素处理导致AVIC群体基础张力丧失,在5 mM KCl水平下,瓣叶刚度分别降低76%(AC,p = 0.001)和54%(WC,p = 0.036),同时如预期的那样,添加90 mM KCl可阻止收缩。我们推测,观察到的AVIC收缩的层依赖性效应主要是由于心室层和纤维层细胞外基质力学特性的差异。此外,虽然我们已经证明AVIC的收缩能力是主动脉瓣瓣叶弯曲刚度的一个重要贡献因素,但它很可能在维持主动脉瓣瓣叶组织内稳态方面发挥作用,这还有待阐明。(c)2004 Elsevier Ltd.保留所有权利。
The aortic valve (AV) leaflet contains a heterogeneous interstitial cell population composed predominantly of myofibroblasts, which contain both fibroblast and smooth muscle cell characteristics. The focus of the present study was to examine aortic valve interstitial cell (AVIC) contractile behavior within the intact leaflet tissue. Circumferential strips of porcine AV leaflets were mechanically tested under flexure, with the AVIC maintained in the normal, contracted, and contraction-inhibited states. Leaflets were flexed both with (WC) and against (AC) the natural leaflet curvature, both before and after the addition of 90 mM KCI to elicit cellular contraction. In addition, a natural basal tonus was also demonstrated by treating the leaflets with 10 mu M thapsigargin to completely inhibit AVIC contraction. Results revealed a 48% increase in leaflet stiffness with AVIC contraction (from 703 to 1040 kPa, respectively) when bent in the AC direction (p = 0.004), while the WC direction resulted only in 5% increase (from 491 to 516.5 kPa, respectively-not significant) in leaflet stiffness in the active state. Also, the loss of basal tonus of the AVIC population with thapsigargin treatment resulted in 76% (AC, p = 0.001) and 54% (WC, p = 0.036) decreases in leaflet stiffness at 5 mM KCI levels, while preventing contraction with the addition of 90 mM KCI as expected. We speculate that the observed layer dependent effects of AVIC contraction are primarily due to varying ECM mechanical properties in the ventricularis and fibrosa layers. Moreover, while we have demonstrated that AVIC contractile ability is a significant contributor to AV leaflet bending stiffness, it most likely serves a role in maintaining AV leaflet tissue homeostasis that has yet to be elucidated. (c) 2004 Elsevier Ltd. All rights reserved.