Endothelial dysfunction in the regulation of cirrhosis and portal hypertension

Abstract

Portal hypertension is caused by an increased intrahepatic resistance, a major consequence of cirrhosis. Endothelial dysfunction in liver sinusoidal endothelial cells (LSECs) decreases the production of vasodilators, such as nitric oxide (NO) and favors vasoconstriction. This contributes to an increased vascular resistance in the intrahepatic/sinusoidal microcirculation. Portal hypertension, once developed, causes endothelial cell (EC) dysfunction in the extrahepatic, i.e. splanchnic and systemic, circulation. Unlike LSEC dysfunction, EC dysfunction in the splanchnic and systemic circulation overproduces vasodilator molecules, leading to arterial vasodilatation. In addition, portal hypertension leads to the formation of portosystemic collateral vessels. Both arterial vasodilatation and portosystemic collateral vessel formation exacerbate portal hypertension by increasing the blood flow through the portal vein. Pathologic consequences, such as esophageal varices and ascites, result. While the sequence of pathological vascular events in cirrhosis and portal hypertension have been elucidated, the underlying cellular and molecular mechanisms causing EC dysfunctions are not yet fully understood. This review article summarizes the current cellular and molecular studies on EC dysfunctions found during the development of cirrhosis and portal hypertension with a focus on intra- and extrahepatic circulation. The article ends by discussing future directions of study for EC dysfunctions.

Serum Proteoglycans as Prognostic Biomarkers of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis

“…Endocan has been proposed as a pertinent biomarker of endothelial dysfunction in severe sepsis (25). Serum endocan may indeed reflect endothelial dysfunction induced by a systemic inflammatory response, a pathologic process that could modify the course of cirrhosis (26). As hepatocellular carcinoma often develops in cirrhotic liver, death from the underlying disease constitutes a competitive risk of death from the tumor.…”

The Molecules: Abnormal Vasculatures in the Splanchnic and Systemic Circulation in Portal Hypertension"

“…Both excessive arterial vasodilation and portosystemic collateral vessel formation help to increase the blood flow through the portal vein and worsen portal hypertension. This facilitates the development of the abnormal hemodynamic condition, called the hyperdynamic circulatory syndrome, and ultimately leads to variceal bleeding and ascites (Bosch 2000;Bosch 2007;Groszmann 1993;Iwakiri 2011;Iwakiri & Groszmann 2006). This chapter summarizes current knowledge of molecules and factors that play critical roles in the development and maintenance of excessive arterial vasodilation and portosystemic collateral vessels in the splanchnic and systemic circulation in cirrhosis and portal 2 hypertension.…”

The Mechanisms of Adaptation of the Vascular Bed to Hemodynamic Changes in Portal Hypertension

“…Возникающие при этом расстройства кровообра-щения обусловлены как эндотелиальной дисфункцией, так и реструктуризацией сосудистого русла, включающей в себя ремоделирование сосудов и ангиогенез [3].…”