Seminar

Sinusoidal cross-talk in liver diseases

Jordi Gracia, PhD

The hepatic microcirculatory status is key for a correct function of the liver. In recent years we have tremendously advanced in understanding the mechanisms underlying the onset of circulatory dysfunction in liver pathologies, such as chronic liver disease and liver transplantation. During the development of cirrhosis, all cellular components of the hepatic vasculature undergo profound changes in their phenotype involving loss of function and/or development of harmful response mechanisms. In fact, chronic liver damage markedly modifies sinusoidal endothelial cells, which lose their vasoprotective phenotype exhibiting pro-thrombotic, pro-inflammatory and vasoconstrictor properties. The liver resident macrophages (Kupffer cells) become pro-inflammatory and pro-vasoconstrictor. Finally, stellate cells proliferate and acquire highly contractile and pro-fibrogenic capacities. These changes occur in a paracrine and very coordinated manner. Similarly, we have recently described the acute damage that liver sinusoidal cells suffer during graft preservation for transplantation, worsening graft viability post-transplantation. A better understanding of the molecular basis of liver microcirculatory dysfunction has allowed the identification of new therapeutic targets and additional pharmacological agents. The seminar will cover the basic pathophysiological events occurring in the sinusoid during the progression of acute and chronic liver diseases, and will include the most promising therapeutic options targeting the liver microcirculation. New experimental models to study the liver vascular biology will be described. Jordi Gracia-Sancho is a Ramón y Cajal Researcher at the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) in Barcelona. He pursued his PhD at the University of Barcelona (2007), and continued his training as postdoctoral research fellow at the Center for Excellence in Vascular Biology – Harvard University. In 2012 he obtained his present position. His research focuses on the vascular biology of the liver in health and diseased conditions, receiving financial support from both national and international institutions. Dr Gracia-Sancho has published 45 peer-review articles, with a mean IF of 9.3 and more than 1500 citations. He serves as Academic editor for Plos One, Associate Editor for Frontiers in Medicine, and peer-reviewer for the main Journals of the field. He is member of the Scientific Committees of the Catalan Association of Digestology (SCD) and the Spanish Association for the Study of the Liver (AEEH), and member of the Steering Committee of the Portal Hypertension Special Interest Group of the American Association for the Study of Liver Diseases (AASLD). In 2016, the European Association for the Study of the Liver (EASL) gave him the Young Investigator Award 2016.