Protein molecule ramps up blood flow

UNC CHAPEL HILL (US) — A protein molecule improves function of cells in patients hospitalized with cardiac arrest, increasing blood flow to organs previously cut off from circulation.

The findings could enhance clinical trials testing endothelial progenitor cells that, when effective, are able to create new blood vessels to bypass blockages that cause heart attacks and peripheral artery disease.

“The premise of these trials is that these cells will supply the ischemic organ with new blood vessels and allow the damaged organ to function better,” says senior study author Arjun Deb,  assistant professor of medicine at the University of North Carolina-Chapel Hill.

“But because you are isolating these cells from the patients themselves, you know that the cells are dysfunctional—so the approach is almost flawed from the very beginning. We want to see how we can improve the function of these cells so they can do their job better.”

The study, published in the Federation of American Societies for Experimental Biology Journal, is the first to show that the Wnt1 protein, one of a family of 19 such molecules, can stimulate blood vessel formation.

A number of studies in the past few years have suggested that genes that play an important role during early development and get “turned off” during adulthood may also get “turned on” or expressed again in response to injury, such as heart attack.

Researchers looked to see if any members of the Wnt family of developmental genes follow the same pattern and found that one gene in particular, Wnt1, was expressed during development of blood vessels, shut off during adulthood and then re-expressed in angiosarcoma, a cancer of endothelial cells.

Deb wanted to see what would happen if he put the Wnt1 protein on human endothelial progenitor cells. Treating them with Wnt1 not only greatly increased their function but also their number.

Next, Deb investigated what effect the protein would have on a mouse model of peripheral artery disease, an illness in humans caused by decreased blood flow to the extremities and found treating the animals with a single injection of the Wnt1 protein resulted in almost three fold increase in blood flow in the affected areas.

“We found that Wnt1 is a novel proangiogenic molecule, something that has never been shown before,” Deb says.

“It gives us hope that injecting the Wnt1 protein—or molecules that stimulate the Wnt1 signaling pathway—into ischemic tissues in humans could improve blood flow and assert a therapeutic effect.”

Approximately 1 in 4 deaths in adults in the US are secondary to heart disease and as many as 15 percent of Americans age 65 and older have peripheral artery disease.

Researchers from the University of Washington, Seattle contributed to the research that was funded by the National Institutes of Health and Ellison Medical Foundation.

Lab-grown human endothelial progenitor cells. (Credit: UNC-Chapel Hill)

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