Mechanism for the formation of new blood vessels discovered

Having a healthy network of blood vessels that bring oxygen and nutrients to tissues, is essential for survival. Blood vessels are lined by cells called endothelial cells that are needed to form the hollow vessel through which blood is channelled to all tissues.

A new study by Chiara Testini and co-workers shows the mechanism whereby new endothelial cells are formed by division of existing cells. Loss of this mechanism, and therefore too few blood vessels, may result in death during embryo development due to inadequate blood vessel supply to the brain. Alternatively, having fewer vessels disturbs organ function after birth.

Interestingly, the importance of this mechanism varies with the genetic composition of the individual. In certain genetic designs, the effect is only seen during embryo development, while in other genetic designs, the effect is seen only after birth.

“We were very surprised to discover the importance of genetics in controlling the mechanism of endothelial cell division. Certain types of mice would not survive embryo development, while others would survive but show defects after birth,” says Chiara Testini, first author of the study which has been a team work headed by Lena Claesson-Welsh.

A protein called vascular endothelial growth factor (VEGF) has long been recognised as a master regulator of endothelial cells. It is known to induce these cells to divide and multiply by affecting activities in the cell nucleus. Exactly how this is controlled has eluded explanation. However, in the present study the researchers demonstrate the involvement of a single amino acid in the receptor protein VEGFR2, which binds VEGF on endothelial cells.

The authors devised experiments using mice that lacked the amino acid in question in the VEGFR2 protein. In these mice, which had everything needed to make new blood vessels expect for the particular amino acid, the cells were no longer able to send signals to the nucleus to cause cell division.

“That such a critical mechanism, formation of new blood vessels, is controlled by a single amino acid was really unexpected and we had to check the results again and again with various techniques. We hope these new findings can be developed to manipulate endothelial cell formation to make more or less blood vessels dependent on the need,” says Lena Claesson-Welsh.

More information:
Article in EMBO Reports
Lena Claesson-Welsh’s research