Mechanotransduction in embryonic vascular development.
Mechanotransduction in embryonic vascular development.
复制标题
胚胎血管发育过程中的机械传导。
DOI：
10.1007/s10237-012-0412-9
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发表时间：
2012-11
影响因子：
3.5
通讯作者：
Pekkan K
中科院分区：
文献类型：
--
作者：
Roman BL;Pekkan K
大量的生物化学信号提供了空间和时间线索，精心编排了脊椎动物胚胎发育的复杂过程。胚胎脉管系统不仅在这些生化线索的背景下发育，而且在血液流动所传递的生物力学力的背景下发育。在成熟的血管系统中，不同的血流机制诱导不同的遗传程序，并且在理解这些力量如何被内皮细胞感知并转导成生化信号方面取得了重大进展。然而，不能假设支配成熟脉管系统的模式与发育中的胚胎脉管系统有关。胚胎血管系统可以对血流的机械力做出反应，这些反应在血管重塑、发芽血管生成的某些方面以及维持动静脉同一性方面至关重要。在这里，我们回顾了内皮细胞机械转导的机制方面的数据，重点是对剪切应力的反应，并详细阐述了剪切应力对胚胎血管系统的各种影响。此外，我们讨论了新兴的预测血管生长模型，并强调了将信号通路信息与计算建模相结合的前景。我们认为，血流动力学参数的精确测量与内皮细胞基因表达和细胞行为的影响之间的相关性是充分理解血流诱导负荷如何控制正常血管发育和形成先天性心血管异常的必要条件。
A plethora of biochemical signals provides spatial and temporal cues that carefully orchestrate the complex process of vertebrate embryonic development. The embryonic vasculature develops not only in the context of these biochemical cues, but also in the context of the biomechanical forces imparted by blood flow. In the mature vasculature, different blood flow regimes induce distinct genetic programs, and significant progress has been made toward understanding how these forces are perceived by endothelial cells and transduced into biochemical signals. However, it cannot be assumed that paradigms that govern the mature vasculature are pertinent to the developing embryonic vasculature. The embryonic vasculature can respond to the mechanical forces of blood flow, and these responses are critical in vascular remodeling, certain aspects of sprouting angiogenesis, and maintenance of arterial-venous identity. Here, we review data regarding mechanistic aspects of endothelial cell mechanotransduction, with a focus on the response to shear stress, and elaborate upon the multifarious effects of shear stress on the embryonic vasculature. In addition, we discuss emerging predictive vascular growth models and highlight the prospect of combining signaling pathway information with computational modeling. We assert that correlation of precise measurements of hemodynamic parameters with effects on endothelial cell gene expression and cell behavior is required for fully understanding how blood flow-induced loading governs normal vascular development and shapes congenital cardiovascular abnormalities.