Atherosclerosis, or hardening of the arteries affects millions of people, and can ultimately cause a stroke or heart attack. The process occurs when fat, cholesterol and other substances build up in the walls of arteries, forming hard particles called plaques. A Miller School investigator, Lina Shehadeh, Ph.D., assistant professor of medicine in the Cardiovascular Division and investigator at the Interdisciplinary Stem Cell Institute and Vascular Biology Institute, has received a National Institutes of Health/National Institute on Aging K01 grant to study how these plaques form, and potentially reverse the process.
The grant of $360,000 over three years is not only a nod to the accelerated research of Shehadeh, but also an honor for the Miller School’s mentorship of her work. On the advisory committee which oversees her progress is Pascal J. Goldschmidt, M.D., Senior Vice President for Medical Affairs and Dean of the Miller School, who describes her work as “inspiring.” Shehadeh is “taking new approaches to discovering what’s behind one of the most common causes of heart attack and stroke.”
The advisory committee also includes Mauro Moscucci, M.D., M.B.A., Interim Chair of Medicine and Chief of the Cardiovascular Division, Omaida Velazquez, M.D., Interim Executive Dean for Research, Research Training and Innovative Medicine, and Chief of the Division of Vascular and Endovascular Surgery, and Si Pham, M.D., professor of surgery and Chief of the Division of Heart and Lung Transplantation.
Joshua Hare, M.D., Director of the Interdisciplinary Stem Cell Institute, and Keith Webster, Ph.D., Director of the Vascular Biology Institute (VBI), are the primary mentors overseeing her work in this field and call it “outstanding.” They are both also the mentors of Shehadeh’s project, Modulation of MicroRNAs in Nicotine-Enhanced Atherogenesis, that was just funded by the State of Florida.
Artery walls and vessels start out as smooth muscle cells, but over time, stem cells can begin growing abnormally. When they start dividing and migrating, plaques form, making it more difficult for blood to flow through them. Those blockages can cause clots to form, further blocking blood flow, and pieces of plaque can actually break off and move to smaller vessels, blocking them entirely.
People who have high cholesterol or are overweight are at high risk for atherosclerosis, and this hardening of the arteries also increases with age. While certain medicines can slow the process, right now, nothing can reverse the formation of plaque once it has occurred.
Shehadeh’s research has focused on how this plaque forms. She identified a molecule, a microRNA that is naturally produced by the body. As people age, less of this microRNA is produced and more plaque forms. Her in vitro and early mouse studies have shown that this microRNA affects the growth of smooth muscle cells, causing them to grow less.
“If we can do this in a dish and a mouse,” said Shehadeh, “then it makes sense to see how this would work in people.” This K01 grant funds the next step, examining how this microRNA affects young and old mice with atherosclerosis.
“This work is extremely exciting,” says Hare, who is leading mesenchymal stem cell research in patients who have suffered heart attacks. “We’re seeing more evidence that we can reverse and prevent damage that we never could before now. More and more we’re seeing evidence that microRNAs regulate stem cells. It is not surprising to me that Lina’s work was so well received at the National Institute of Aging.”
Webster agrees that Shehadeh, who was awarded the “Stop Heart Disease Researchers of the Year Award” by the Florida Heart Research Institute for her work in RNA therapy, is at the “forefront of finding a way to truly impact the lives of patients. The VBI is here to support excellent science like Lina’s, and help get funding for anyone who does research in the areas of vascular biology or vascular disease.”
Shehadeh says this grant will help her determine if this microRNA will act like a statin, reducing cholesterol and plaque. “The hope is to develop this into a drug that people can benefit from.”