Role of mechanotransduction in vascular biology: focus on thoracic aortic aneurysms and dissections.
Role of mechanotransduction in vascular biology: focus on thoracic aortic aneurysms and dissections.
复制标题
DOI：
10.1161/circresaha.114.304936
复制
发表时间：
2015-04-10
影响因子：
20.1
通讯作者：
Milewicz DM
中科院分区：
文献类型：
--
作者：
Humphrey JD;Schwartz MA;Tellides G;Milewicz DM
涉及进行性扩大、急性夹层或破裂的胸主动脉疾病受到血流动力学负荷和壁的机械特性的影响。然而，我们对导致这些潜在致命状况的机械生物学过程了解有限。稳态需要壁内细胞感知其局部化学机械环境并建立、维持、重塑或修复细胞外基质以提供适当的顺应性和足够的强度。反过来，正确的传感需要将细胞外基质连接到细胞内肌动球蛋白丝的受体和将相关信息传递到细胞核的信号分子。胸主动脉瘤和夹层与高血压控制不佳以及细胞外基质成分、膜受体、收缩蛋白和相关信号分子的基因突变有关。这组因素表明，这些胸部疾病部分是由于壁内细胞对细胞外基质的机械感应和机械调节功能失调造成的，这导致了壁的结构完整性受损。因此，提高对主动脉细胞力学生物学的理解可能会导致胸主动脉瘤和夹层的新治疗策略。
Thoracic aortic diseases that involve progressive enlargement, acute dissection, or rupture are influenced by the hemodynamic loads and mechanical properties of the wall. We have only limited understanding, however, of the mechanobiological processes that lead to these potentially lethal conditions. Homeostasis requires that intramural cells sense their local chemo-mechanical environment and establish, maintain, remodel, or repair the extracellular matrix to provide suitable compliance and yet sufficient strength. Proper sensing, in turn, necessitates both receptors that connect the extracellular matrix to intracellular actomyosin filaments and signaling molecules that transmit the related information to the nucleus. Thoracic aortic aneurysms and dissections are associated with poorly controlled hypertension and mutations in genes for extracellular matrix constituents, membrane receptors, contractile proteins, and associated signaling molecules. This grouping of factors suggests that these thoracic diseases result, in part, from dysfunctional mechanosensing and mechanoregulation of the extracellular matrix by the intramural cells, which leads to a compromised structural integrity of the wall. Thus, improved understanding of the mechanobiology of aortic cells could lead to new therapeutic strategies for thoracic aortic aneurysms and dissections.