In-situ deformation of the aortic valve interstitial cell nucleus under diastolic loading
In-situ deformation of the aortic valve interstitial cell nucleus under diastolic loading
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DOI：
10.1115/1.2801670
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发表时间：
2007-12-01
影响因子：
1.7
通讯作者：
Sacks, Michael S.
中科院分区：
文献类型：
--
作者：
Huang, Hsiao-Ying Shadow;Liao, Jun;Sacks, Michael S.
主动脉瓣（AV）瓣叶内存在一群间质细胞（AVIC），它们通过蛋白质合成和酶降解来维持组织结构的完整性。AVIC的典型特征是肌成纤维细胞，表现出表型可塑性，并可能在瓣膜病理生理学中发挥重要作用。虽然已知AVIC可以在体外对机械刺激作出反应，但体内AVIC变形的水平及其与心动周期期间局部胶原纤维重定向的关系仍然未知。在本研究中，使用猪AV戊二醛固定在0-90 mm Hg跨瓣压力下，研究AVIC的变形。由此产生的核纵横比（NAR）的变化被用作整体细胞应变的指数，并对空间位置和压力负荷水平的依赖性进行量化。还使用小角度光散射定量相同瓣膜中的局部胶原纤维排列。组织水平的有限元（FE）模型的AVIC嵌入在AV细胞外基质也被用来探索AV组织和细胞水平的变形之间的关系。结果表明，AVIC NAR随跨瓣压（例如，从0 mm Hg时的平均值1.8到90 mm Hg时的平均值4.8），以及明显的层特异性依赖性。胶原纤维排列的相关变化表明，对于低于类似于1 mm Hg的压力，随着大量纤维拉直，几乎没有AVIC变形发生，随后AVIC NAR从4 mm Hg大幅增加至90 mm Hg。虽然组织级有限元模型能够捕捉到定性响应，但它也低估了中航工业变形的程度。这一结果表明，额外的微机械和纤维压实的影响发生在高压水平。本研究的结果形成的基础上，了解跨瓣压力介导的机械转导内的天然AV和第一次定量数据AVIC核变形与AV组织。显微组织和变形
Within the aortic valve (AV) leaflet resides a population of interstitial cells (AVICs), which serve to maintain tissue structural integrity via protein synthesis and enzymatic degradation. AVICs are typically characterized as myofibroblasts, exhibit phenotypic plasticity, and may play an important role in valve pathophysiology. While it is known that AVICs can respond to mechanical stimuli in vitro, the level of in vivo AVIC deformation and its relation to local collagen fiber reorientation during the cardiac cycle remain unknown. In the present study, the deformation of AVICs was investigated using porcine AV glutaraldehyde fixed under 0-90 mm Hg transvalvular pressures. The resulting change in nuclear aspect ratio (NAR) was used as an index of overall cellular strain, and dependencies on spatial location and pressure loading levels quantified. Local collagen fiber alignment in the same valves was also quantified using small angle light scattering. A tissue-level finite element (FE) model of an AVIC embedded in the AV extracellular matrix was also used explore the relation between AV tissue- and cellular-level deformations. Results indicated large, consistent increases in AVIC NAR with transvalvular pressure (e.g., from mean of 1.8 at 0 mm Hg to a mean of 4.8 at 90 mm Hg), as well as pronounced layer specific dependencies. Associated changes in collagen fiber alignment indicated that little AVIC deformation occurs with the large amount of fiber straightening for pressures below similar to 1 mm Hg, followed by substantial increases in AVIC NAR from 4 mm Hg to 90 mm Hg. While the tissue-level FE model was able to capture the qualitative response, it also underpredicted the extent of AVIC deformation. This result suggested that additional micromechanical and fiber-compaction effects occur at high pressure levels. The results of this study form the basis of understanding transvalvular pressure-mediated mechanotransduction within the native AV and first time quantitative data correlating AVIC nuclei deformation with AV tissue. microstructure and deformation.