Research

Area 3

Hepatic hemodynamics and portal hypertension

Team leader

  • Joan C. García-Pagán
    (Hospital Clínic)

Strategic objectives

Translational research aimed at furthering knowledge on the pathophysiology of portal hypertension, which is the main complication in chronic liver disease. Discovering new therapeutic targets, introduction of new treatments for this syndrome and development of new noninvasive techniques for its clinical evaluation.

The group also works in the fields of vascular disorders of the liver, abnormal angiogenesis in liver disease, and conservation of organs.

Main lines of research

  1. Factors that regulate liver microcirculation under normal conditions and in the context of cirrhosis, using studies in animal models of cirrhosis, in perfusion systems in the isolated liver and in sinusoidal endothelial cells and hepatic stellate cells.
  2.   Study and regulation of the phenotype of cells that make up liver sinusoids: importance in the pathophysiology of portal hypertension, in conservation of the liver ex vivo, in complications of cirrhosis and in ageing.
  3. Protection of the liver from external injury in healthy and cirrhotic livers.
  4. Angiogenesis in chronic liver disease: function, up-regulation/down-regulation and therapeutic potential.
  5. Obesity in chronic liver disease: pathogenic mechanisms and therapeutic implications.
  6. Molecular and cellular regulation of the progression of fatty liver in cirrhosis and cancer of the liver: identification of new therapeutic targets.
  7. Clinical studies of random distribution of new treatments for portal hypertension. 
  8. Vascular liver disease (Budd-Chiari syndrome, portal thrombosis, and idiopathic portal hypertension).
  9.   Prevention of decompensated cirrhosis.
  10.   Discovery of diagnostic biomarkers for idiopathic portal hypertension and for risk stratification. 

Research Group

Regulation of liver microcirculation in cirrhosis and in vascular liver disease

Juan Carlos García-Pagán

(group leader: HCB)

Virginia Hernández-Gea (PI-HCB)
Montserrat Marí (PI-CSIC)
Àngels Escorsell (PI-HCB)

Portal hypertension is one of the most serious complications of liver disease and, while cirrhosis of the liver is the most common cause of portal hypertension in our setting, a group of diseases covered by the umbrella term of noncirrhotic portal hypertension, though less frequent, often affect young people and are associated with considerable levels of morbidity and mortality. The research of our group, which consists of 3 PIs, focuses on understanding pathophysiology, new invasive and noninvasive diagnostic methods, and research on new treatment strategies for portal hypertension in cirrhotic and noncirrhotic portal hypertension, specifically in Budd-Chiari syndrome, noncirrhotic portal thrombosis and idiopathic portal hypertension. One of our strategic areas of research is the study of abnormal pathophysiology in the intrahepatic microcirculation in cirrhosis that causes increased portal pressure. We focus on studying the phenotypic regulation of endothelial liver cells and their interaction with other liver cells, mainly with hepatic stellate cells, and their role in the genesis of hepatic fibrosis and their potential modulation to design new therapeutic strategies for treating portal hypertension. To achieve these goals, our group uses molecular biology, cell isolation and culture, perfusion of organs, immune staining, cytometry, and mass analysis of omic data, light and electron microscopy, etc. Furthermore, our group has, for years, been a benchmark center for the diseases that cause noncirrhotic portal hypertension and we are involved in multiple studies at both the basic and clinical level for improving understanding for prognosis, diagnosis, and evaluation of new treatment strategies.

Research Group

Angiogenesis in liver disease

Mercedes Fernández Lobato

(IDIBAPS)

Our research (http://www.mercedesfernandezlab.com) focuses on identifying the causes of and factors that control chronic liver disease, such as cirrhosis of the liver and liver cancer, which affect millions of humans and are the main causes of death and liver transplants worldwide. This is essential in order to fully understand the unresolved pathogenic mechanisms of the disease and facilitate the identification of new therapeutic routes to improving human health. Our specific research projects include the following: (1) Angiogenesis in chronic liver disease: function, up-regulation/down-regulation and therapeutic potential; (2) Obesity in chronic liver disease: pathogenic mechanisms and therapeutic implications; (3) Molecular and cellular regulation of the progression of fatty liver in cirrhosis and cancer of the liver: identification of new therapeutic targets.

Research Group

Vascular biology of the liver

Jordi Gracia-Sancho

(IDIBAPS)

The cells that make up liver microcirculation, principally sinusoidal endothelial cells, stellate cells and resident macrophages (Kupffer cells), play a key role in the development and progression of liver disease, and therefore represent an important therapeutic target for the treatment and improvement of patients with liver damage. Our research group studies the molecular and biomechanical processes that regulate the phenotype of these sinusoidal cells, and hepatic intercellular communication mechanisms, in healthy persons, in response to acute liver damage, in chronic liver disease (cirrhosis and fatty liver), and in ageing. We use the results of our research to develop new therapies that improve microcirculation, fibrosis and liver function. In order to achieve our goals, we use a wide range of experimental methods that include tissues and primary cells, both human and rodent, in vivo/in vitro models of liver disease, cell co-culture by means of liver-on-a-chip technology, and mass analysis of omic data.