Department of Translational Medical Sciences, University of Campania "L. Vanvitelli", Naples, Italy.
Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada.
Prog Cardiovasc Dis. 2020 Jul-Aug;63(4):465-474. doi: 10.1016/j.pcad.2020.06.009. Epub 2020 Jun 26.
The aortopathy associated with bicuspid aortic valve (BAV) is an epidemiologically relevant source of chronic and acute aortic disease (aneurysm and dissection). However, its pathogenesis is still the object of scientific uncertainties and debates. Indeed, the mechanisms determining the diseases of the ascending aorta in BAV patients are most likely complex and multifactorial, i.e. resulting from variable modes of interplay between genetic and hemodynamic factors. Although few scientific studies have so far taken into adequate account this complexity, leaving the precise sequence of pathogenetic events still undiscovered, the accumulated evidence from previous research approaches have at least brought about important insights. While genetic studies have so far identified variants relevant to either valve malformation or aortic complications (including those in the genes NOTCH1, TGFBR2, ACTA2, GATA5, NKX2.5, SMAD6, ROBO4), however each explaining not more than 5% of the study population, other investigations have thoroughly described both the flow features, with consequent forces acting on the arterial wall (including skewed flow jet direction, rotational flow, wall shear stress), and the main changes in the molecular and cellular wall structure (including extracellular matrix degradation, smooth muscle cell changes, oxidative stress, unbalance of TGF-β signaling, aberrant endothelial-to-mesenchymal transition). All of this evidence, together with the recognition of the diverse phenotypes that the aortopathy can assume in BAV patients, holding possible prognostic significance, is reviewed in this chapter. The complex and multifaceted body of knowledge resulting from clinical and basic science studies on BAV aortopathy has the potential to importantly influence modes of clinical management of this disease in the near future.
与二叶式主动脉瓣（BAV）相关的主动脉病变是慢性和急性主动脉疾病（动脉瘤和夹层）的一个具有流行病学相关性的来源。然而，其发病机制仍然是科学不确定性和争论的对象。事实上，决定 BAV 患者升主动脉疾病的机制很可能是复杂的和多因素的，即来自遗传和血流动力学因素之间相互作用的可变模式。尽管到目前为止，很少有科学研究充分考虑到这种复杂性，使得致病事件的精确序列仍然未知，但以前研究方法的累积证据至少带来了重要的见解。虽然遗传研究迄今为止已经确定了与瓣膜畸形或主动脉并发症相关的变异体（包括 NOTCH1、TGFBR2、ACTA2、GATA5、NKX2.5、SMAD6、ROBO4 基因中的变异体），但每个变异体仅能解释研究人群的 5% 以内，其他研究还彻底描述了血流特征，以及随之对动脉壁产生的力（包括偏流射流方向、旋转流、壁切应力），以及分子和细胞壁结构的主要变化（包括细胞外基质降解、平滑肌细胞变化、氧化应激、TGF-β 信号转导失衡、异常的内皮向间充质转化）。所有这些证据，以及对 BAV 患者的主动脉病变可能具有预后意义的不同表型的认识，都在本章中进行了回顾。从 BAV 主动脉病变的临床和基础科学研究中得出的复杂和多方面的知识体系，有可能在不久的将来重要地影响这种疾病的临床管理模式。
