Department of Biomedical Engineering, The University of Akron, Akron, OH, United States.
Independent Consultant, Austin, TX, United States.
Acta Biomater. 2018 Feb;67:248-258. doi: 10.1016/j.actbio.2017.11.040. Epub 2017 Dec 2.
Quantifying mechanically-induced changes in the tricuspid valve extracellular matrix (ECM) structural components, e.g. collagen fiber spread and distribution, is important as it determines the overall macro-scale tissue responses and subsequently its function/malfunction in physiological/pathophysiological states. For example, functional tricuspid regurgitation, a common tricuspid valve disorder, could be caused by elevated right ventricular pressure due to pulmonary hypertension. In such patients, the geometry and the normal function of valve leaflets alter due to chronic pressure overload, which could cause remodeling responses in the ECM and change its structural components. To understand such a relation, we developed an experimental setup and measured alteration of leaflet microstructure in response to pressure increase in porcine tricuspid valves using the small angle light scattering technique. The anisotropy index, a measure of the fiber spread and distribution, was obtained and averaged for each region of the anterior, posterior, and septal leaflet using four averaging methods. The average anisotropy indices (mean ± standard error) in the belly region of the anterior, posterior, and septal leaflets of non-pressurized valves were found to be 12 ± 2%, 21 ± 3% and 12 ± 1%, respectively. For the pressurized valve, the average values of the anisotropy index in the belly region of the anterior, posterior, and septal leaflets were 56 ± 5%, 39 ± 7% and 32 ± 5%, respectively. Overall, the average anisotropy index was found to be higher for all leaflets in the pressurized valves as compared to the non-pressurized valves, indicating that the ECM fibers became more aligned in response to an increased ventricular pressure.
Mechanics plays a critical role in development, regeneration, and remodeling of tissues. In the current study, we have conducted experiments to examine how increasing the ventricular pressure leads to realignment of protein fibers comprising the extracellular matrix (ECM) of the tricuspid valve leaflets. Like many other tissues, in cardiac valves, cell-matrix interactions and gene expressions are heavily influenced by changes in the mechanical microenvironment at the ECM/cellular level. We believe that our study will help us better understand how abnormal increases in the right ventricular pressure (due to pulmonary hypertension) could change the structural architecture of tricuspid valve leaflets and subsequently the mechanical microenvironment at the ECM/cellular level.
定量分析三尖瓣细胞外基质（ECM）结构成分的机械诱导变化，例如胶原纤维的展开和分布，这很重要，因为它决定了整体宏观组织反应，进而决定了其在生理/病理状态下的功能/故障。例如，功能性三尖瓣反流是一种常见的三尖瓣疾病，可能是由于肺动脉高压导致右心室压力升高引起的。在这些患者中，由于慢性压力超负荷，瓣叶的几何形状和正常功能发生改变，这可能导致 ECM 发生重塑反应并改变其结构成分。为了理解这种关系，我们开发了一种实验装置，并使用小角度光散射技术测量了猪三尖瓣在压力升高时瓣叶微观结构的变化。通过四种平均方法，获得了各前叶、后叶和隔叶区域的各向异性指数（纤维展开和分布的度量），并对其进行了平均。在未加压瓣膜的前叶、后叶和隔叶的腹部区域，未加压瓣膜的平均各向异性指数（平均值±标准误差）分别为 12±2%、21±3%和 12±1%。对于加压瓣膜，前叶、后叶和隔叶腹部区域的各向异性指数平均值分别为 56±5%、39±7%和 32±5%。总体而言，与未加压瓣膜相比，加压瓣膜所有瓣叶的平均各向异性指数均升高，表明 ECM 纤维在心室压力增加时变得更加对齐。
力学在组织的发育、再生和重塑中起着关键作用。在本研究中，我们进行了实验，以研究增加心室压力如何导致三尖瓣瓣叶细胞外基质（ECM）中的蛋白纤维重新排列。与许多其他组织一样，在心脏瓣膜中，细胞-基质相互作用和基因表达在很大程度上受到 ECM/细胞水平机械微环境变化的影响。我们相信，我们的研究将帮助我们更好地理解右心室压力（由于肺动脉高压）的异常增加如何改变三尖瓣瓣叶的结构结构，进而改变 ECM/细胞水平的机械微环境。
