Blister-forming protein helps build blood vessels

How does the body go about generating blood vessels? This question has been studied by a research team from Uppsala University in collaboration with colleagues from the National Institutes of Health in the United States. The findings show that a relatively unknown protein, CLIC4, forms blisters that later develop into the hollow interior of the vessel. The study is being published in the December 23 issue of Journal of Biological Chemistry.

The scientists in the project mapped what proteins change in different ways in connection with the formation of tubular structures, such as blood vessels. It turned out that a large number of proteins changed, and the researchers were able to determine the identity of 27 of them. The most exciting of these proteins is called CLIC4, intracellular chloride channel No. 4.

Not much is known about CLIC4, but studies of a related protein in roundworms show that it participates in the formation of the worm¹s excretion canal. There are several indications that tubular structures are created in a similar manner in primitive organisms and humans.

An important phase in this formation of a tube is the generation of tiny blisters, vesicles, inside the cell. These blisters merge into larger so-called vacuoles, which are the preliminary stages of the hollow interior of the tube. The research team from Uppsala and the United States investigated where CLIC4 is found in blood vessel cells and found the protein in the walls of tiny vesicles inside the cell. Then the scientists saw that the protein is to be found in certain vessels in tumors, where vessels are constantly being generated.

“This indicates that CLIC4 is involved in the formation of vessels,” says Lena Claesson Welsh.

By inhibiting the capacity of blood vessel cells to produce CLIC4, the research team was able to show that the protein is needed for a blood vessel to be created.

“This is entirely new information. Previously it was not known what proteins regulate the process when vesicles merge into vacuoles to form the hollow interior of vessels,” Lena Claesson Welsh explains.

Intensive research is underway to find out how blood vessels are generated. If we can understand how the tubes are created, we will be able to design better drugs to stop the production of vessels, which is of relevance to a number of diseases, such as cancer, diabetes, and chronic inflammations.