Ming He, M.D., Ph.D.About half of Americans between the ages of 45 and 84 live with atherosclerosis without knowing it. Atherosclerosis is a disease that develops when plaque builds in the arteries, narrowing blood flow and sometimes leading to dangerous clots. This condition is linked to diseases like heart disease — the leading cause of death in the United States.
Ming He, M.D., Ph.D., an assistant professor at the University of Alabama at Birmingham’s Marnix E. Heersink School of Medicine Department of Pathology Division of Molecular and Cellular Pathology, is leading two recently funded studies to investigate the pathobiology of atherosclerosis and explore ways to prevent it before damage is caused.
“Atherosclerosis often starts where blood vessels branch or curve, which can cause changes in blood flow and damage to the vessel lining,” He said. “We recently discovered a new change in cells that appears under disturbed blood flow conditions, which affects how the cells work. This finding may help explain how outside factors can alter cell activity and play a role in the development of this disease.”
He received funding from the National Institutes of Health’s National Heart, Lung and Blood Institute for his first project, titled “Unveiling the Atheroprone Role of Novel Mechanosensitive Histone Modification.” The five-year, $2.7 million study will run through May 2030.
“This research will help us understand how blood vessel cells malfunction, how atherosclerosis is initiated and how epigenetic mechanisms operate in endothelial cells, while also challenging current patterns of histone modifications in health and disease,” He said.
He received additional funding from the National Institute of Diabetes and Digestive and Kidney Diseases for his project titled “Histone H3 O-GlcNAcylation in Endothelial Cells Promotes Diabetic Vascular Complications.” The four-year, $2.3 million study will run through August 2029.
With this grant, He and his team found that high blood sugar can alter histone structure and create a cellular memory, making certain genes more easily activated when a “second hit,” such as increased fatty food intake, occurs, ultimately accelerating atherosclerosis. This environment-induced cellular memory may help explain the interaction between environmental and genetic components and shed light on the link between metabolic disorders and cardiovascular disease.
“The first study focuses on epigenetic regulation in the initiation of atherosclerosis, while the second project examines epigenetic memory in disease progression,” He said. “We hope our work will advance understanding of this novel epigenetic regulation in atherosclerosis and ultimately improve human health.”