Liver vascular biology

Problem

Liver diseases represent a serious social problem, with a health prevalence comparable to that of respiratory diseases. By way of example, over the last ten years, chronic liver disease, also known as cirrhosis, has led to the death of more than 35,000 men and 10,000 women in Spain.

The cells that are part of the liver’s blood vessels, mainly sinusoidal endothelial cells, stellate cells and resident macrophages, play a key role in the development and progression of liver disease. Therefore, they can be therapeutic targets to be taken into account for the treatment and improvement of patients with liver damage.

Approach

The group studies the molecular and biomechanical processes that regulate the status and function of these sinusoidal cells, as well as hepatic intercellular communication mechanisms in health situations, in response to acute liver damage, in chronic liver disease (cirrhosis and steatohepatitis) and in ageing.

The results obtained are applied to discover new therapeutic targets and to develop new therapies that improve microcirculation, fibrosis and liver function. To achieve this, the group uses a wide range of experimental methods, which include tissues and primary cells (humans or rodents), models of liver disease in vivo and in vitro, cellular culture through liver-on-a-chip technology and mass analysis of omics data, among others.

Impact

The group has discovered the KLF2 autophagy pathway as a key mechanism in the regulation of liver cell health. It is a finding that proposes the use of statins, which activate this pathway, as components for the treatment of cirrhosis, both in the early and very advanced stages.

In the field of ageing, it has described the changes suffered by liver microcirculation in situations of old age, both in health and acute liver damage as well as during chronic liver disease. These advances have shown that the protective agent, simvastatin, would be useful in the subpopulation of older patients.

Finally, in the field of new technologies, it has developed the first human liver-on-a-chip. This innovation has already been transferred to a company and, therefore, has been placed at the service of society.