Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT, USA Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT, USA
J R Soc Interface. 2014 Aug 6;11(97):20140397. doi: 10.1098/rsif.2014.0397.
The medial layer of large arteries contains aggregates of the glycosaminoglycan hyaluronan and the proteoglycan versican. It is increasingly thought that these aggregates play important mechanical and mechanobiological roles despite constituting only a small fraction of the normal arterial wall. In this paper, we offer a new hypothesis that normal aggregates of hyaluronan and versican pressurize the intralamellar spaces, and thereby put into tension the radial elastic fibres that connect the smooth muscle cells to the elastic laminae, which would facilitate mechanosensing. This hypothesis is supported by novel computational simulations using two complementary models, a mechanistically based finite-element mixture model and a phenomenologically motivated continuum hyperelastic model. That is, the simulations suggest that normal aggregates of glycosaminoglycans/proteoglycans within the arterial media may play equally important roles in supporting (i.e. a structural role) and sensing (i.e. an instructional role) mechanical loads. Additional simulations suggest further, however, that abnormal increases in these aggregates, either distributed or localized, may over-pressurize the intralamellar units. We submit that these situations could lead to compromised mechanosensing, anoikis and/or reduced structural integrity, each of which represent fundamental aspects of arterial pathologies seen, for example, in hypertension, ageing and thoracic aortic aneurysms and dissections.
大动脉的中层含有糖胺聚糖透明质酸和蛋白聚糖 versican 的聚集物。尽管这些聚集物仅构成正常动脉壁的一小部分，但它们在机械和机械生物学中发挥着重要作用，这一观点正日益得到认可。在本文中，我们提出了一个新的假设，即正常的透明质酸和 versican 聚集物会对板层间空间施加压力，从而使连接平滑肌细胞和弹性层的径向弹性纤维产生张力，这有助于机械感受器感知。这一假设得到了两种互补模型（基于力学的有限元混合物模型和基于现象的连续超弹性模型）的新计算模拟的支持。也就是说，模拟表明，动脉中层中正常的糖胺聚糖/蛋白聚糖聚集物可能在支持（即结构作用）和感知（即指令作用）机械负荷方面发挥同样重要的作用。然而，进一步的模拟表明，这些聚集物的异常增加（无论是分布性的还是局部性的），可能会过度加压板层间单位。我们认为，这些情况可能导致机械感受器感知能力下降、失巢凋亡和/或结构完整性降低，这些都是高血压、衰老和胸主动脉瘤及夹层等动脉病变的基本方面。
