A study discovered that single cells in the innermost layer of blood vessels proliferate after injury and in so doing make a significant contribution to the formation of new vessels. Researchers have now been able to shed light on this process. They have shown that single cells in the innermost layer of blood vessels proliferate after injury and in so doing make a significant contribution to the formation of new vessels.

Observation in the living organism and especially in the heart of how new blood vessels form is not possible in mammals. However, little is known to date about the actual process of new vessel formation, although this knowledge could contribute in future to remedying tissue damage, such as occurs in diabetes or following an ischemia-induced heart attack.

Clonal expansion after a heart attack

In damaged heart tissue following a heart attack, the researchers were able to observe that certain cells had divided repeatedly. They also detected this cell division, which is referred to as clonal expansion, in damaged tissue in skeletal muscles caused by ischemia. To do so, they analyzed the fluorescence in endothelial cells in tissue slices taken from the damaged areas. They found the ratio of clonally expanding cells between 30 and 50% very surprising. 

In new-born models, by contrast, Professor Dimmeler and her team did not observe any clonal expansion in the formation of new vessels in the retina. It would, therefore, seem that the growth of blood vessels during normal development results from the random multiplication and integration of cells. This result coincides with observations in zebrafish, in which what is known as "cell mixing" also plays an important role in the formation of new blood vessels during development.

Cell profiling

The researchers were keen to characterize the dividing cells more precisely, and to this purpose, they analyzed which genes are transcribed in single examples of the clonally expanding endothelial cells. "Surprisingly, we found a large number of gene products that are typical for the transition from an endothelial to a mesenchymal cell," says Dimmeler. This transition, or EndMT process, is a contributor to many pathogenic processes, such as scarring.

In endothelial cells, the gene products typical for EndMT do not, however, mirror a transition but instead presumably just an intermediate stage that enables the cells to detach themselves from the cell assembly to multiply.

Clonal expansion as a possible therapy for heart attack patients

Researcher now wants to know about the clonally expanded cells in the long term, since at present they are only able to track their fate for about two months. They want to know what has happened to these cells after a year and whether the new blood vessels are just as good as the old ones in the long term.

They might be that clonal expansion is no longer that efficient in older people, which is why a lot of damaged tissue dies off after a heart attack and forms scar tissue which cannot be reactivated through the formation of new blood vessels. If they manage to characterize the clonally expanding cells more precisely, they will hopefully find ways to re-stimulate this process.