Role of vasodilation in liver regeneration and health

Role of vasodilation in liver regeneration and health
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血管舒张在肝脏再生和健康中的作用

DOI:
10.1515/hsz-2021-0155
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发表时间:
2021
影响因子:
3.7
通讯作者:
E. Lammert
E. Lammert
中科院分区:
生物学2区
文献类型:
--
作者:
Linda Große;E. Lammert

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最近,我们已经证明,通过肝脏的血流量增强会触发肝细胞增殖,从而促进肝脏生长。在这篇综述中,我们首先解释了关于肝部分切除术(PHx)后肝血流及其变化的文献,然后我们介绍了PHx引起的初始血流动力学改变后肝脏再生的不同步骤。随后对与肝血管系统直接相关的控制肝脏再生的分子机制进行了综述。这些包括肝窦内皮细胞(LSECs)中β1整合素依赖的机械转导,触发机械诱导的血管内皮生长因子受体-3 (VEGFR3)和基质金属蛋白酶-9 (MMP9)的激活以及促进生长的血管分泌信号的释放。最后,我们推测高龄和肥胖如何对肝脏血管系统产生负面影响,从而影响肝脏的再生和健康,我们总结了最近在临床上应用肝脏灌注的一些技术进展。总之,肝血管的力学弹性特性和改变是更好地理解和影响肝脏健康、再生和疾病的关键。
Abstract Recently, we have shown that an enhanced blood flow through the liver triggers hepatocyte proliferation and thereby liver growth. In this review, we first explain the literature on hepatic blood flow and its changes after partial hepatectomy (PHx), before we present the different steps of liver regeneration that take place right after the initial hemodynamic changes induced by PHx. Those parts of the molecular mechanisms governing liver regeneration, which are directly associated with the hepatic vascular system, are subsequently reviewed. These include β1 integrin-dependent mechanotransduction in liver sinusoidal endothelial cells (LSECs), triggering mechanically-induced activation of the vascular endothelial growth factor receptor-3 (VEGFR3) and matrix metalloproteinase-9 (MMP9) as well as release of growth-promoting angiocrine signals. Finally, we speculate how advanced age and obesity negatively affect the hepatic vasculature and thus liver regeneration and health, and we conclude our review with some recent technical progress in the clinic that employs liver perfusion. In sum, the mechano-elastic properties and alterations of the hepatic vasculature are key to better understand and influence liver health, regeneration, and disease.
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期刊: NATURE
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