Protein promotes the growth of small arteries on damaged heart tissue in mice, according to a study – ScienceDaily

Kristy Red-Horse, PhD, badociate professor of biology, and Joseph Woo, MD, professor of cardiothoracic surgery, believe that the growth of these new arteries could help heal the damage caused by heart disease or heart attack, or even prevent this damage.

In clinical practice, Woo observed that the results of blocked patients in the large arteries feeding the heart were often very different. "Some patients are stuck in a coronary artery and die, other patients are stranded in multiple areas, but can run marathons," said Woo, Norman E. Shumway Chair.

The difference, says Woo, is perhaps that this second group of patients has collateral arteries, tiny arteries that bypbad the obstructions of the main arteries of the heart and fuel the areas of the heart deprived of oxygen.

"They're like the side streets that allow you to get around a traffic jam on the highway," said Woo. Such collateral arteries could help people with atherosclerosis or those who are recovering from a heart attack, except that collateral arteries are only visible in a minority of patients.

Now, Woo, Red-Horse, and their colleagues have discovered how these collateral arteries and a signaling molecule that promote their growth in adult mice are formed, offering hope that collateral arteries may be able to grow in human patients. .

Their conclusions will be published on January 24 in Cell. Red-Horse, a member of the Stanford Institute of Stem Cell and Regenerative Medicine, and Woo, a member of the Stanford Institute of Cardiology, share the author's responsibility. Postdoctoral fellows Soumyashree Das, PhD, and Andrew Goldstone, MD, PhD, are the lead co-authors.

Studying newborn mice

The researchers began by examining newborn mice. "Neonatal mice have a robust ability to heal injured heart tissue, but they're no longer able to heal in adulthood," Red-Horse said. "Understand why could identify ways to boost regeneration in adults."

They documented that the healing of young mice was due in part to the growth of new collateral arteries in the injured area. Through advanced imaging allowing them to look at intact newborn hearts at the cellular level, the researchers showed that this was due to the fact that arterial endothelial cells were leaving the artery, migrating along existing capillaries extending into the injured heart tissue and gathered to form collateral arteries.

The researchers then studied how the cells could do it. Red-Horse and Woo knew that the CXCL12 molecule was an important signal during the embryonic development of arterial cells and was shown to improve heart recovery and function after a heart attack. Scientists have wondered whether this molecule has a beneficial effect in promoting the growth of collateral arteries in the injured heart tissue. They found that CXCL12 was mainly restricted to arterial endothelial cells in the hearts of uninjured neonatal mice. In newborn mice with cardiac lesions, it appears in the capillaries of the injured area. The researchers found evidence that low levels of oxygen in the injured area activated the genes that create CXCL12, signaling the areas to which arterial endothelial cells should migrate.

CXCL12 test in adult mice

Next, they examined whether CXCL12 could help adult heart tissue to develop collateral arteries. "Our studies have shown that adults' hearts do not form collateral arteries like newborns do after injury," Red-Horse said. After causing heart attacks in adult mice, they injected CXCL12 into the injured areas. Indeed, 15 days after the wounds, there were numerous new collateral arteries formed by the stinging and migrating artery cells. Almost none was present in the control mice.

Red-Horse and Woo think that the complete story is not so simple. "We believe that there is a whole series of proteins that support cell migration off the arteries and promote cell proliferation among damaged cells," Red-Horse said. Nevertheless, they hope that this discovery can become the basis of a new therapy.

"The question now is whether this mechanism we have discovered can be therapeutically manipulated to generate collateral arteries in human patients," said Woo.