The missing ingredient to develop blood vessels

Researchers at the University of Virginia's Faculty of Medicine have discovered an essential ingredient in the proper formation of blood vessels that accounts for the failure of many promising treatments. The discovery provides an important direction for efforts to better treat a host of serious diseases ranging from diabetes to heart attacks and strokes.

Until now, scientists seeking to develop blood vessels focused almost exclusively on the growth of the inner layer of blood vessels, consisting of endothelial cells. The hope was that these endothelial cells would then recruit all the other types of cells needed to form a complete and functional blood vessel. Researchers led by Gary K. Owens, Ph.D., director of the Robert M. Berne Cardiovascular Research Center (UVA), have determined that these vessels can only grow properly when they are grown in conjunction with one another. cell type, called perivascular cells. , including smooth muscle cells and pericytes. The researchers compare these perivascular cells to the outer support layers of a rubber hose or car tires, without which they could burst or leak.

"Most studies on angiogenesis [blood vessel formation] focused on the inner lining of the pipes themselves, "said researcher Daniel L. Hess. This is pretty well understood. But you do not really understand how to get a complete functional blood vessel that can withstand the mechanical force of blood pressure. "

The new discovery of UVA helps answer this question and, in doing so, saves scientists from the time, effort and cost involved in implementing treatment strategies that ultimately will not bear fruit.

The discovery was made possible by the fortuitous convergence of research in two different laboratories at UVA. Hess was working on a model of Peripheral Artery Disease in Owens Laboratories and Dr. Brian Annex, of the UVA Research Center of the Robert M. Bern Cardiovascular Research Center, while another Researcher, Molly R. Kelly-Goss, was working with a model of blood vessel growth that she developed in the laboratory of Shayn M. Peirce, Ph.D., of the Department of Biomedical Engineering at the University of Michigan. UVA.

By combining these two models, the researchers were able to determine the vital role of perivascular cells in the formation of blood vessels and identify a gene, Oct4, necessary for this process. Previously, it was thought that Oct4 was active only in embryonic stem cells early in development and that it was permanently inactivated in adult organisms. This idea lasted until two years ago, when the Owens laboratory showed that it was reactivated within smooth muscle cells during the formation of atherosclerotic plaques in the blood vessels and needed for training a protective fibrous cap on the lesions preventing them from breaking and causing the heart attack or stroke – similar to a crest on a tire. The lab has now shown that Oct4 plays an important role in the formation of the vessels themselves, which is ironically necessary to form the outer wall of blood vessel protection.

Using the Kelly-Goss model, researchers were able to examine the formation of blood vessels in real time. They found that vessels without coverage by perivascular cells were incompletely formed and leaked. "Many unsuccessful trials have assumed that perivascular cells were just passive followers," Owens said. But without them, he said, "the whole process stops". Importantly, they found that endothelial cells and perivascular cells communicate with each other via Oct4-dependent processes and that otherwise, blood vessels or functional blood vessel networks can not form.

In the end, this means that scientists need to take a more sophisticated approach to the growth of new vessels, an important process for normal growth and reproduction as well as for wound repair.

Provided by
University of Virginia