Iwakiri Yasuko, Shah Vijay, Rockey Don C
The Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United States.
The Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States.
J Hepatol. 2014 Oct;61(4):912-24. doi: 10.1016/j.jhep.2014.05.047. Epub 2014 Jun 6.
Chronic liver disease is associated with remarkable alterations in the intra- and extrahepatic vasculature. Because of these changes, the fields of liver vasculature and portal hypertension have recently become closely integrated within the broader vascular biology discipline. As developments in vascular biology have evolved, a deeper understanding of vascular processes has led to a better understanding of the mechanisms of the dynamic vascular changes associated with portal hypertension and chronic liver disease. In this context, hepatic vascular cells, such as sinusoidal endothelial cells and pericyte-like hepatic stellate cells, are closely associated with one another, where they have paracrine and autocrine effects on each other and themselves. These cells play important roles in the pathogenesis of liver fibrosis/cirrhosis and portal hypertension. Further, a variety of signaling pathways have recently come to light. These include growth factor pathways involving cytokines such as transforming growth factor β, platelet derived growth factor, and others as well as a variety of vasoactive peptides and other molecules. An early and consistent feature of liver injury is the development of an increase in intra-hepatic resistance; this is associated with changes in hepatic vascular cells and their signaling pathway that cause portal hypertension. A critical concept is that this process aggregates signals to the extrahepatic circulation, causing derangement in this system's cells and signaling pathways, which ultimately leads to the collateral vessel formation and arterial vasodilation in the splanchnic and systemic circulation, which by virtue of the hydraulic derivation of Ohm's law (pressure = resistance × flow), worsens portal hypertension. This review provides a detailed review of the current status and future direction of the basic biology of portal hypertension with a focus on the physiology, pathophysiology, and signaling of cells within the liver, as well as those in the mesenteric vascular circulation. Translational implications of recent research and the future directions that it points to are also highlighted.
慢性肝病与肝内和肝外血管系统的显著改变相关。由于这些变化，肝脏血管系统和门静脉高压领域最近在更广泛的血管生物学学科中紧密结合。随着血管生物学的发展，对血管过程的更深入理解使得人们对与门静脉高压和慢性肝病相关的动态血管变化机制有了更好的认识。在这种背景下，肝血管细胞，如窦状内皮细胞和类周细胞样肝星状细胞，彼此紧密相关，它们相互之间以及自身具有旁分泌和自分泌作用。这些细胞在肝纤维化/肝硬化和门静脉高压的发病机制中起重要作用。此外，最近发现了多种信号通路。这些包括涉及细胞因子如转化生长因子β、血小板衍生生长因子等的生长因子通路，以及多种血管活性肽和其他分子。肝损伤的一个早期且持续的特征是肝内阻力增加；这与肝血管细胞及其信号通路的变化相关，进而导致门静脉高压。一个关键概念是，这个过程将信号聚集到肝外循环，导致该系统细胞和信号通路紊乱，最终导致内脏和体循环中的侧支血管形成和动脉血管舒张，根据欧姆定律的水力推导（压力=阻力×流量），这会加重门静脉高压。本综述详细回顾了门静脉高压基础生物学的现状和未来方向，重点关注肝脏内以及肠系膜血管循环中的细胞生理学、病理生理学和信号传导。还强调了近期研究的转化意义及其所指向的未来方向。
