Atkins Samantha K, Cao Kai, Rajamannan Nalini M, Sucosky Philippe
Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN, USA.
Biomech Model Mechanobiol. 2014 Nov;13(6):1209-25. doi: 10.1007/s10237-014-0567-7. Epub 2014 Mar 6.
The type-I bicuspid aortic valve (BAV), which differs from the normal tricuspid aortic valve (TAV) most commonly by left-right coronary cusp fusion, is frequently associated with secondary aortopathies. While BAV aortic dilation has been linked to a genetic predisposition, hemodynamics has emerged as a potential alternate etiology. However, the link between BAV hemodynamics and aortic medial degeneration has not been established. The objective of this study was to compare the regional wall shear stresses (WSS) in a TAV and BAV ascending aorta (AA) and to isolate ex vivo their respective impact on aortic wall remodeling. The WSS environments generated in the convex region of a TAV and BAV AA were predicted through fluid-structure interaction (FSI) simulations in an aorta model subjected to both valvular flows. Remodeling of porcine aortic tissue exposed to TAV and BAV AA WSS for 48 h in a cone-and-plate bioreactor was investigated via immunostaining, immunoblotting and zymography. FSI simulations revealed the existence of larger and more unidirectional WSS in the BAV than in the TAV AA convexity. Exposure of normal aortic tissue to BAV AA WSS resulted in increased MMP-2 and MMP-9 expressions and MMP-2 activity but similar fibrillin-1 content and microfibril organization relative to the TAV AA WSS treatment. This study confirms the sensitivity of aortic tissue to WSS abnormalities and demonstrates the susceptibility of BAV hemodynamic stresses to focally mediate aortic medial degradation. The results provide compelling support to the important role of hemodynamics in BAV secondary aortopathy.
I型二叶式主动脉瓣（BAV）与正常三叶式主动脉瓣（TAV）的不同之处主要在于左右冠状动脉瓣叶融合，常伴有继发性主动脉病变。虽然BAV主动脉扩张与遗传易感性有关，但血流动力学已成为一种潜在的替代病因。然而，BAV血流动力学与主动脉中膜退变之间的联系尚未确立。本研究的目的是比较TAV和BAV升主动脉（AA）中的局部壁面剪应力（WSS），并在体外分离它们对主动脉壁重塑的各自影响。通过在承受两种瓣膜血流的主动脉模型中进行流固耦合（FSI）模拟，预测TAV和BAV AA凸面区域产生的WSS环境。通过免疫染色、免疫印迹和酶谱分析，研究猪主动脉组织在锥板生物反应器中暴露于TAV和BAV AA WSS 48小时后的重塑情况。FSI模拟显示，BAV中存在比TAV AA凸面更大且更单向的WSS。与TAV AA WSS处理相比，正常主动脉组织暴露于BAV AA WSS导致MMP-2和MMP-9表达增加以及MMP-2活性增加，但原纤维蛋白-1含量和微原纤维组织相似。本研究证实了主动脉组织对WSS异常的敏感性，并证明了BAV血流动力学应力对局部介导主动脉中膜退变的易感性。结果为血流动力学在BAV继发性主动脉病变中的重要作用提供了有力支持。
