Research

Area 3

Liver hemodynamics and portal hypertension. Digestive bleeding secondary to ruptured esophageal varicose veins.

Team leader

Strategic objectives

The gaining of in-depth knowledge of the mechanisms underlying portal hypertension – the main complication of liver diseases – and development of new treatments for this syndrome, and new noninvasive assessment techniques.

Main lines of research


1. Factors regulating liver microcirculation under normal conditions and in cirrhosis, based on isolated liver perfusion studies and studies in liver sinusoid endothelial
cells.

2. Intrahepatic endothelial dysfunction in liver cirrhosis.

3. Post-transcriptional regulation of endothelial nitric oxide synthase (eNOS) activity. Relevance in the treatment of portal hypertension.

4. Regulation of the transcription of liver sinusoid endothelial cell protecting genes: relevance in the physiopathology of portal hypertension and in ex vivo liver preservation.

5. Regulation of the development of collateral circulation, hyperdynamic circulation and liver fibrogenesis by angiogenic factors.

6. New noninvasive methods for evaluating cirrhosis.

7. Randomized clinical studies of novel treatments for portal hypertension.

8. Hepatic vascular diseases.

Grups

Regulation of liver microcirculation in cirrhosis and hepatic vascular diseases (Associated)

GARCIA-PAGAN, JUAN CARLOS

(ICMDM)

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. Part of this increase is dynamic and amenable to modification by means of drugs. Therefore, improved knowledge based on experimental models in animals of the cellular, biochemical and molecular mechanisms regulating this dynamic component 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.

Angiogenesis in liver diseases (Associated)

Merce Fernadez Lobato

We focus our research on the implication and regulation of angiogenesis in the physiopathology of portal hypertension. Recent studies in experimental models of portal hypertension have shown that angiogenesis or the formation of new blood vessels is crucial to two of the most important components of the physiopathology of portal hypertension: the formation of portosystemic collateral vessels and the development of hyperdynamic splanchnic circulation.

The results of these studies may contribute valuable information with a view to improving our knowledge of the molecular mechanisms implicated in the physiopathology of portal hypertension and chronic liver diseases – these being a leading cause of mortality and an important indication for liver transplantation both in this country and worldwide. Our aim is that the studies of this project can lead to the development of new therapeutic approaches designed to reduce the morbidity and mortality of patients diagnosed with these disorders.