Lipids in Health and Disease

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of unknown aetiology affecting the large bile ducts and characterized by periductal fibrosis and stricture formation, which ultimately result in biliary cirrhosis and liver failure. Arteriosclerosis involves the accumulation of altered lipids and lipoproteins in large arteries; this drives inflammation and fibrosis and ultimately leads to narrowing of the arteries and hypoperfusion of dependent organs and tissues. Knowledge of the causative factors is crucial to the understanding of disease mechanisms and the development of specific treatment. Based on pathogenetic similarities between PSC and arteriosclerosis, we hypothesize that PSC represents "arteriosclerosis of the bile duct" initiated by toxic biliary lipids. This hypothesis is based on common molecular, cellular, and morphological features providing the conceptual framework for a deeper understanding of their pathogenesis. This hypothesis should stimulate translational research to facilitate the search for novel treatment strategies for both diseases. Background Arteriosclerosis, a disease of the large arteries, represents the single most important contributor to total disease burden in developed countries [1,2]. From a pathomorphological point of view, arteriosclerosis is characterized by smooth muscle cell hyperplasia or hypertrophy and matrix protein accumulation in the vessel intima and media, with lipid deposition leading to thickening and induration of the arterial wall and subsequently to arterial stenosis. Over the past decade, attention has become focused on the critical link between modified lipids and lipid products and the initiation and perpetuation of inflammation in arteriosclerosis [3,4]. PSC, a disease of the large bile ducts with a poor median survival of 12 years, is characterised by chronic bile duct inflammation leading to biliary fibrosis and finally cirrhosis. It is often complicated by cholangiocarcinoma (10– 15%) [5]. Due to the overall costs to society related to its morbidity, mortality, and need for liver transplantation, PSC in young adults and cholangiopathies in general are increasingly recognized as very important liver diseases [6]. The lack of effective medical treatments for PSC may be deeply rooted in the lack of understanding of the disease mechanisms of PSC. Based on similar pathogenetic features and mediators found in both entities (summarized in Table 1 and displayed in Figure 1 and 2, we postulate that PSC shares common disease mechanisms with arteriosclerosis vice versa which may become therapeutic targets in the near future in both diseases. Published: 25 January 2007 Lipids in Health and Disease 2007, 6:3 doi:10.1186/1476-511X-6-3 Received: 17 November 2006 Accepted: 25 January 2007 This article is available from: http://www.lipidworld.com/content/6/1/3 © 2007 Fickert et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.