For the first time, scientists at Uppsala University have uncovered a key mechanism responsible for forming new blood vessels. The study revealed the mechanism whereby the division of existing cells forms new endothelial cells. This mechanism may lead to death during embryo development due to an inadequate oxygen supply to the brain.
Fascinatingly, the significance of this mechanism changes with the individual’s genetic composition. In specific genetic designs, the effect is just observed during embryo development, while in other genetic designs, the effect is seen simply after birth.
Chiara Testini, the first author of the study, said, “We were amazed to discover the importance of genetics in controlling the mechanism of endothelial cell division. Certain mice would not survive embryo development, while others would survive but show defects after birth.”
A vascular endothelial growth factor (VEGF) protein has long been recognized 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. Precisely 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 lacking the amino acid in the VEGFR2 protein. In these mice, which had everything needed to make new blood vessels except for the particular amino acid, the cells could no longer send signals to the nucleus to cause cell division.
Lena Claesson-Welsh, Professor at the Department of Immunology, Genetics, and Pathology, Uppsala University, Sweden, said, “That such a critical mechanism, formation of new blood vessels, is controlled by a single amino acid was unexpected, and we had to check the results, again and again, using various techniques. We hope these new findings can be developed to manipulate endothelial cell formation to make more or fewer blood vessels dependent on the need.”
The new study is published in the journal EMBO Reports.