Sydney Medical School, University of Sydney, NSW, Australia.
Int J Cardiol. 2013 Oct 25;169(1):7-16. doi: 10.1016/j.ijcard.2013.08.056. Epub 2013 Aug 27.
Thoracic aortic aneurysm and dissection in young and middle aged patients is increasingly recognised as due to genetic aortopathy. Mutations in multiple genes affecting proteins in the extracellular matrix, microfibrillar structure, the endothelium and cell signalling pathways have been associated with thoracic aortic disease. The TGFß signalling pathway appears to play a key role in mediating abnormal aortic growth and aneurysm formation. A challenge remains in understanding how the many different gene mutations can result in deranged TGFß signalling. This review examines the functional relationships between key structural and signalling proteins, with reference to the need for maintenance of homeostasis in mechanotransduction within the aortic wall. A mechanism, through which perturbations in mechanotransduction, arising from different gene mutations, results in altered TGFß signalling is described.
胸主动脉瘤和夹层在年轻和中年患者中越来越被认为是由于遗传性主动脉病。多个基因的突变，这些基因影响细胞外基质、微纤维结构、内皮和细胞信号通路中的蛋白质，与胸主动脉疾病有关。TGFß 信号通路似乎在介导主动脉异常生长和动脉瘤形成中发挥关键作用。目前仍面临的一个挑战是理解许多不同的基因突变如何导致 TGFß 信号的紊乱。这篇综述检查了关键结构和信号蛋白之间的功能关系，并参考了在主动脉壁内机械转导中维持内稳态的需要。描述了一种机制，通过该机制，来自不同基因突变的机械转导的扰动导致 TGFß 信号的改变。
