Research

Area 3

Hepatic hemodynamics and portal hypertension

Team leader

Strategic objectives

Translational research aimed at advancing in the Knowledge of the pathophysiology of portal hypertension the main complication of chronic liver diseases, discovery of new therapeutic targets, introduction of new treatments for this syndrome, and development of new noninvasive techniques for its clinical evaluation. In addition, the group is active in the fields of vascular liver diseases, angiogenesis abnormalities in liver disease and on organ preservation.

Main lines of research

  1. Factors regulating liver microcirculation under normal conditions and in cirrhosis, based on isolated liver perfusion studies and studies in isolated liver sinusoid endothelial cells.
  2. Regulation of the transcription of liver sinusoid endothelial cell protecting genes: relevance in the physiopathology of portal hypertension, in ex vivo liver preservation and in the complications of cirrhosis.
  3. Liver protection from external injury in healthy and cirrhotic livers.
  4. Angiogenesis and portal hypertension: contribution to the regulation of the development of collateral circulation, hyperdynamic circulation and liver fibrogenesis.
  5. New noninvasive methods for evaluating cirrhosis.
  6. Randomized clinical studies of novel treatments for portal hypertension.
  7. Hepatic vascular diseases.
  8. Prevention of decompensation of cirrhosis.
  9. Discovery of diagnostic biomarkers for idiophatic portal hypertension and for risk-stratification. 

Research Group

Regulation of liver microcirculation in cirrhosis and hepatic vascular diseases

Juan Carlos García-Pagán

(HCB)

One of the mechanisms responsible for the development of portal hypertension and its serious consequences is the increase in portal resistance observed within the cirrhotic liver. Improved knowledge based on experimental models in animals of the cellular, biochemical and molecular mechanisms regulating the mechanisms involved in the increased intrahepatic resistance in cirrhosis and the potential mechanisms to modulate them will allow us to design new strategies for the treatment of these disorders.

Liver vascular disorders, particularly Budd-Chiari syndrome and non-cirrhotic portal thrombosis, are infrequent causes of portal hypertension. This complicates progress in our knowledge of these illnesses, their prognosis and treatments. This circumstance is of particular relevance, since these diseases mainly affect young patients with a potentially long life expectancy. For a number of years, our group has served as a reference center for these illnesses – thus allowing us to propose new treatment options and to advance in furthering our knowledge.

Research Group

Angiogenesis in liver diseases

Mercedes Fernández Lobato

(IDIBAPS)

Our research group investigates the role of angiogenesis, that is, the formation of new blood vessels, in the pathophysiology of chronic liver diseases, which affect millions of human beings all over the world. In the course of our research, we have demonstrated that angiogenesis is a crucial pathological hallmark of chronic liver disease, which contributes to the development and maintainance of portal hypertension, hyperdynamic splanchnic circulation, and postosystemic collateralization, and is also closely linked to fibrogenesis and inflammation in the cirrhotic liver. Much of our work is now devoted to understanding the molecular and cellular mechanisms that regulate the angiogenic process. This is essential to fully elucidate the pathological functions of angiogenesis, and to facilitate the identification of new and more effective therapeutic strategies, which, by inhibiting or attenuating angiogenesis, could be potentially useful to reduce the morbility and mortality of patients suffering from chronic liver diseases. This is of particular significance since the incidence of chronic liver disease is increasing in the world’s population and the therapeutic options are limited. Our approach is multidisciplinary and employs a variety of animal models of liver diseases in rat and mouse, genetically engineered mouse models, established mammalian cell lines, samples of liver tissue from patients with liver disease, in vivo hemodynamic studies in animals, in vitro cell culture studies, tissue histology and immunohistochemistry, and biochemical, cellular and molecular biology strategies.

www.mercedesfernandezlab.com

Research Group

Liver vascular biology

Jordi Gracia-Sancho

(IDIBAPS)

Cells that compose the hepatic microcirculation, mainly sinusoidal endothelial, stellate and Kupffer cells, play an essential role in the development and progression of liver diseases, and therefore represent a key therapeutic target to treat patients with liver pathologies. Our research team studies the biology of these sinusoidal cells, and their interactions, in health and in front of an acute or chronic liver injury, both in young and aged individuals, to ultimately develope novel therapeutic approaches to ameliorate liver microcirculation, fibrosis and hepatic function. To accomplish our aims we use a variety of translational models, which include the study of tissue and primary cells from humans, experimental models in rodents, and cellular co-culture using advanced liver-on-a-chip technology.