Role of vasodilation in liver regeneration and health.

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 ß1 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.