The Role of the Renin-Angiotensin System in Hepatic Fibrosis

Abstract

The liver is the second largest organ of the body and has a multitude of functions including carbohydrate and fatty acid metabolism, lipid transport, protein synthesis, storage of fat-soluble vitamins as well as detoxification and modification of compounds absorbed from the small intestine. It has a dual blood supply, with approximately 75% coming from the portal vein and 25% from the hepatic artery. The primary functional unit of the liver, the hepatic lobule, consists of a hexagonal zone of hepatic parenchyma surrounding a central hepatic vein with a number of portal tracts at the periphery which contain a terminal portal vein, bile ductule and hepatic arteriole. In the normal liver, blood flows from portal venous branches through specialised vascular channels called hepatic sinusoids, into the centrilobular hepatic vein. Hepatic sinusoids lack a distinct basement membrane and their endothelial cells have fenestrations which permit bidirectional free passage of solutes between the sinusoid and a sub-sinusoidal space known as the space of Disse. Hepatocytes, account for 70% of liver mass. These cells, which have microvilli on their basolateral surface to facilitate the interchange of nutrients with the sinusoid, are responsible for most of the metabolic and synthetic functions of the liver. Chronic liver diseases disturb the normal structure and function of the liver by initiating hepatic fibrosis, a process that can eventually lead to progressive destruction of the normal hepatic architecture, loss of functioning hepatocytes and the development of liver cirrhosis. Angiotensin II, the main effector peptide of the renin-angiotensin system (RAS), is known to play an important role in chronic tissue injury and fibrosis in cardiovascular disease, chronic renal disease and diabetes. Its