Investigating America’s No. 1 Killer

Ron Korthuis, PhD

Studying microscopic cells in blood vessels that are thinner than a human hair, Ron Korthuis, PhD, has a very big job. He investigates cardiovascular disease, the leading cause of death in Missouri and the nation. In February 2015, the National Institutes of Health (NIH) awarded Korthuis and his research team a $1.7 million grant to examine a biochemical signaling pathway shown to be helpful for patients suffering from heart attacks or strokes.

Ethanol, which is present in alcoholic beverages such as wine and beer, kick starts a sequential series of biochemical steps that reduces tissue damage that occurs when the blood supply is re-established to organs that had their blood supply blocked off, as occurs in diseases such as heart attacks and strokes.

Korthuis is leading the study, “Daily Moderate Ethanol Ingestion Attenuates Postischemic Microvascular Dysfunction,” funded by the National Institute on Alcohol Abuse and Alcoholism.

“If we can understand the biochemical steps that are activated by ethanol to promote cell survival, we could possibly develop a rationale for new drug therapy that people could take all the time, and it would render them resistant to a heart attack or stroke — or if they did suffer one, they’d have less injury,” Korthuis said. “These new drugs would hopefully mimic the beneficial cardioprotective effects of ethanol, while avoiding the negative psychosocial and pathologic effects that can occur with consumption of alcoholic beverages.”

inflamed venule and surrounding tissue
With high-powered microscopes, researchers can see extremely small parts of the body’s microcirculation. This image, captured by researcher Steven Segal, PhD, shows an inflamed venule and surrounding tissue. Segal is a Margaret P. Mulligan Distinguished Professor in Medical Research, Physiology and Education at MU.

Korthuis holds the George L. and Melna A. Bolm Distinguished Chair in Cardiovascular Health and is professor and chair of the School of Medicine’s Department of Medical Pharmacology and Physiology. The department is ranked in the top quarter of similar departments at more than 100 medical schools in terms of research grant funding.

“A strong medical pharmacology and physiology department is vital to determining how human cardiovascular disease develops, and to developing new ways to treat and prevent heart and blood vessel disease,” said William Fay, MD, the J.W. and Lois Winifred Stafford Distinguished Chair in Diabetes and Cardiovascular Research and the director of the Division of Cardiovascular Medicine at MU.

Korthuis’ research team studies the smallest blood vessels in the body, collectively known as the microcirculation. They use intravital microscopy, a high-tech way of observing these very tiny vessels in real-time during reperfusion, or the process of restoring blood flow after a period of ischemia (reduced blood flow to a tissue). The scientists are able to record videos of the microscopic images to further study inflammation in the microcirculation during ischemia and during reperfusion.

This technology is housed in the School of Medicine’s medical pharmacology and physiology laboratories, but the researchers are not confined by the medical school’s walls. Researchers in the department often collaborate with scientists and depend on resources at MU’s Dalton Cardiovascular Research Center, College of Veterinary Medicine, College of Engineering, and Christopher S. Bond Life Sciences Center for expertise and advanced tools for high-resolution imaging and analysis.

“MU has the strongest environment for collaboration of anywhere in the world that I have visited,” Korthuis said. “There is a genuine interest to do things for the good of science and ultimately for the good of patients.”