Aggarwal Ankush, Ferrari Giovanni, Joyce Erin, Daniels Michael J, Sainger Rachana, Gorman Joseph H, Gorman Robert, Sacks Michael S
Center for Cardiovascular Simulation, Institute for Computational Engineering Sciences and the Department of Biomedical Engineering, The University of Texas at Austin, 201 East 24th Street, ACES 5.438, One University Station, C0200, Austin, TX, 78712-0027, USA.
Ann Biomed Eng. 2014 May;42(5):986-98. doi: 10.1007/s10439-014-0973-0. Epub 2014 Feb 1.
The bicuspid aortic valve (AV) is the most common cardiac congenital anomaly and has been found to be a significant risk factor for developing calcific AV disease. However, the mechanisms of disease development remain unclear. In this study we quantified the structure of human normal and bicuspid leaflets in the early disease stage. From these individual leaflet maps average fiber structure maps were generated using a novel spline based technique. Interestingly, we found statistically different and consistent regional structures between the normal and bicuspid valves. The regularity in the observed microstructure was a surprising finding, especially for the pathological BAV leaflets and is an essential cornerstone of any predictive mathematical models of valve disease. In contrast, we determined that isolated valve interstitial cells from BAV leaflets show the same in vitro calcification pathways as those from the normal AV leaflets. This result suggests the VICs are not intrinsically different when isolated, and that external features, such as abnormal microstructure and altered flow may be the primary contributors in the accelerated calcification experienced by BAV patients.
二叶式主动脉瓣（AV）是最常见的心脏先天性异常，并且已被发现是发生钙化性主动脉瓣疾病的一个重要危险因素。然而，疾病发展的机制仍不清楚。在本研究中，我们对疾病早期阶段的人类正常和二叶式瓣叶结构进行了量化。从这些单个瓣叶图谱中，使用一种基于样条的新技术生成了平均纤维结构图谱。有趣的是，我们发现正常瓣膜和二叶式瓣膜之间在统计学上存在不同且一致的区域结构。观察到的微观结构的规律性是一个惊人的发现，特别是对于病理性二叶式主动脉瓣瓣叶而言，并且是任何瓣膜疾病预测数学模型的重要基石。相比之下，我们确定从二叶式主动脉瓣瓣叶分离出的孤立瓣膜间质细胞与从正常主动脉瓣瓣叶分离出的细胞表现出相同的体外钙化途径。这一结果表明，分离出来的瓣膜间质细胞本质上并无差异，并且诸如异常微观结构和改变的血流等外部特征可能是二叶式主动脉瓣患者加速钙化的主要促成因素。
