Researchers at the University of North Carolina (UNC) at Chapel Hill have discovered that Wnt1 improves endothelial progenitor cells' ability to create new blood vessels to bypass blockages that cause heart attacks and peripheral artery disease. The discovery is expected to enhance clinical trials already testing these powerful cells in patients hospitalized with cardiac arrest.
“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,” explains senior study author Arjun Deb, M.D., assistant professor of medicine at the UNC School of Medicine. “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. “
Details of Dr. Deb's study are reported in “Wnt1 is a proangiogenic molecule, enhances human endothelial progenitor function, and increases blood flow to ischemic limbs in a HGF-dependent manner,” published online February 14 in FASEB.
Studies in recent years suggested that genes that play an important role during early development but get turned off during adulthood may also get expressed again in response to a heart attack or other injury. Dr. Deb, who studies the Wnt family of developmental genes, found that Wnt1 was expressed during development of blood vessels, shut off during adulthood, and then re-expressed in angiosarcoma, a cancer of endothelial cells.
Dr. Deb and his colleagues then found that treating human endothelial progenitor cells with Wnt1 not only greatly increased their function but also their number. And after examining the protein on a mouse model of peripheral artery disease, the researchers determined that treating these animals with a single injection of the Wnt1 protein resulted in almost three fold increase in blood flow in the affected areas.
Dr. Deb says future research will include identifying small molecules or drug candidates that could reverse the endothelial progenitor cell dysfunction observed in many patients with vascular disease.