Cyron C J, Wilson J S, Humphrey J D
Department of Biomedical Engineering, Yale University, New Haven, CT, USA
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
J R Soc Interface. 2014 Nov 6;11(100):20140680. doi: 10.1098/rsif.2014.0680.
Static and dynamic mechanical instabilities were previously suggested, and then rejected, as mediators of aneurysmal development, which leaves open the question of the underlying mechanism. In this paper, we suggest as a new paradigm the interpretation of aneurysms as mechanobiological instabilities. For illustrative purposes, we compare analytical calculations with computational simulations of the growth and remodelling of idealized fusiform abdominal aortic aneurysms and experimental and clinical findings. We show that the concept of mechanobiological stability is consistent with the impact of risk factors such as age, smoking or diabetes on the initiation and enlargement of these lesions as well as adaptive processes in the healthy abdominal aorta such as dilatation during ageing or in hypertension. In general, high stiffness, an increased capacity for stress-mediated matrix production, and slow matrix turnover all improve the mechanobiological stability of blood vessels. This theoretical understanding may help guide prognosis and the development of future therapies for aneurysms as it enables systematic ways to attenuate enlargement.
静态和动态机械不稳定性此前曾被认为是动脉瘤发展的介导因素，但随后被否定，这使得潜在机制的问题悬而未决。在本文中，我们提出将动脉瘤解释为机械生物学不稳定性这一新范式。为便于说明，我们将理想化的梭形腹主动脉瘤生长和重塑的解析计算与计算模拟以及实验和临床发现进行了比较。我们表明，机械生物学稳定性的概念与年龄、吸烟或糖尿病等风险因素对这些病变的起始和扩大的影响以及健康腹主动脉中的适应性过程（如衰老或高血压期间的扩张）是一致的。一般来说，高刚度、应力介导的基质产生能力增加以及基质周转缓慢都能提高血管的机械生物学稳定性。这种理论认识可能有助于指导动脉瘤的预后和未来治疗的发展，因为它提供了系统的方法来减轻动脉瘤的扩大。
