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The project led by Steve Lim, Ph.D., is aimed at reducing plaque-building macrophages by inhibiting focal adhesion kinase activity.

Published Sep 14th, 2021

By Casandra Andrews

Researchers at the USA College of Medicine are seeking ways to better understand diseases that narrow blood vessels such as atherosclerosis so more effective treatments can be developed for the disorders that lead to heart disease, heart attacks, strokes and thousands of deaths each year.

Atherosclerosis causes arteries to narrow, weaken and become rigid. As it progresses, fats, cholesterols and other substances known as plaque build up in and on artery walls. Macrophages are a major cell that accumulates these lipids and forms the plaque. As the plaque increases, it reduces the amount of blood and oxygen being delivered to the body’s vital organs. The plaque also can rupture, triggering a blood clot that causes strokes and heart attacks.

Steve Lim, Ph.D., associate professor of biochemistry and molecular biology at the USA College of Medicine recently was awarded a four-year $1.54 million grant to evaluate a potential new treatment for those with atherosclerosis, the chronic inflammatory disease.

Current lipid-lowering drug therapies, such as statins, have proven beneficial for some patients but not all of those suffering from atherosclerosis.

Lim’s new study is aimed at reducing plaque-building macrophages by inhibiting focal adhesion kinase (FAK) activity. Usual cytoplasmic FAK activity promotes macrophage migration in the artery wall. The lab’s recent research found that FAK catalytic inhibition induces nuclear FAK localization from the cytoplasm. The novelty of this project is that nuclear FAK reduces gene expression required for macrophage lipid accumulation and plaque formation.

“There is a real need to develop new therapies to treat a larger portion of atherosclerosis patients and reduce the number of people who die from cardiovascular diseases,” Lim said. “This grant will allow our lab to expand our research and potentially save countless lives.”

Despite advances in medicine, atherosclerotic disease remains a leading cause of death around the world. In the United States, coronary artery disease causes one of every six deaths, accounting for more than 400,000 deaths annually.

A postdoctoral fellow in Lim’s lab, James Murphy, Ph.D., has been a key player in the research group leading this project. The work will be performed with Lim’s other collaborators, Richard Honkanen, Ph.D., professor and chair in the department of biochemistry and molecular biology, and Erin Ahn, Ph.D., associate professor in the department of pathology at the University of Alabama at Birmingham.

Awarded by the National Heart, Lung and Blood Institute, this is Lim’s second research project grant since joining USA. In 2017, he was awarded a $1.52 million four-year grant from the National Institutes of Health to study cell signaling that contributes to atherosclerosis.

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