Institute of Metabolic Physiology, Heinrich Heine University, D-40225 Düsseldorf, Germany.
Institute for Vascular and Islet Cell Biology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University, D-40225 Düsseldorf, Germany.
Biol Chem. 2021 Apr 27;402(9):1009-1019. doi: 10.1515/hsz-2021-0155. Print 2021 Aug 26.
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.
最近，我们已经证明，增强的肝血流会触发肝细胞增殖，从而促进肝脏生长。在这篇综述中，我们首先解释肝血流及其在部分肝切除（PHx）后的变化的文献，然后介绍 PHx 引起的初始血液动力学变化后发生的不同的肝再生步骤。接下来，我们将回顾与肝血管系统直接相关的调控肝再生的分子机制的各个部分。其中包括在肝窦内皮细胞（LSEC）中依赖β1 整联蛋白的力学转导，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，以及生长促进的旁分泌信号的释放。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，进而影响肝脏再生和健康，并总结了最近在临床中采用肝脏灌注方面的一些技术进展。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。
