When there is an increase in pressure within the portal vein, this is known as Portal Hypertension. Portal vein is the vein that carries blood from the digestive organs to the liver. Increased pressure in the portal vein causes large veins to develop across the esophagus and stomach to get around the blockage.
Often, people don’t experience any symptoms until serious damage. When serious damage occurs, the liver becomes scarred, causing fluid to build up in the abdomen and other detrimental side effects, including death.
In a new study, Yale scientists identified the genetic cause of unexplained portal hypertension by performing genomic analysis. Nine patients were evaluated during the study.
Scientists found that each patient had a rare alteration in the same GIMAP5 gene. After replicating the study on mice models, scientists determined that recessive GIMAP5 genotypes resulted in the loss of normal GIMAP5 function.
The gene was found to be a significant regulator of liver endothelial cell homeostasis. The absence of this gene causes portal hypertension.
Silvia Vilarinho, MD, Ph.D., assistant professor of medicine (digestive diseases), and of pathology, said, “This is very exciting. The excitement is to be going from patients that we didn’t know why they develop portal hypertension to identify a novel gene. This new information led us to determine what liver cell is affected and uncover that portal hypertension in these patients resulted from alterations in liver endothelium. Since similar endothelial cell changes are seen in common forms of liver disease, these findings have the potential to translate into therapeutics for chronic liver disease.”
- Kaela Drzewiecki et al. GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension. DOI: 10.1084/jem.20201745