American Heart Association fellowship supports study of protein linking obesity and heart disease

At home in Australia, Mark Renton started playing football as soon as he could. He figured it would eventually lead to a career prescribing strength training and exercise regimens to athletes.

But as an undergraduate, the sports science curriculum included an exercise metabolism course that explored how cells turn energy into movement. This biological focus captured Renton's imagination, and he became increasingly interested in the mechanisms that underly muscle function, including developing force through contractions that mediate precise movements. Ultimately, Renton wound up earning a doctorate studying the heart, the body's most vital muscle.

Now continuing his heart research at the Fralin Biomedical Research Institute at VTC, Renton has received a postdoctoral fellowship from the American Heart Association to study coronary microvascular dysfunction.

When most people think of heart disease, they think of heart attacks. But subtle cardiac problems can arise long before the first chest pain. In coronary microvascular disease, damaged blood vessels are impaired, which reduces blood flow to the heart. One condition puts patients at a particularly increased risk: obesity.

Renton will use the fellowship funding to continue studying the function of a particular protein, pannexin-1, that could hold the key to understanding obesity's effects on heart health. "Pannexin-1 is a channel," said Renton, who works in the lab of Scott Johnstone. "It sits on the outer surface of the cell membrane and allows ions to pass in and out of the cell and even into neighboring cells. These ions can initiate signaling processes within the cell, essentially telling the cell what it needs to do."

The link between obesity and heart disease is long established, but the Johnstone lab team recently discovered that when pannexin-1 is removed, blood vessels in the heart lose their ability to expand and contract properly - a symptom that also occurs in obesity.

This loss of function can lead to blood vessel spasms and chest pain. Renton hopes to uncover whether the loss in function occurs because obesity leads to fewer pannexin-1 channels, changes how the channels function, or alters the signals they transmit.

If we can understand exactly how obesity disrupts these channels, we might be able to develop treatments that keep them working properly - potentially preventing heart problems before they start."

Mark Renton, Fralin Biomedical Research Institute at VTC 

The implications could be far-reaching, as blood vessels throughout our bodies use similar mechanisms to control blood flow. "Obesity doesn't just affect the heart," Renton said. "It affects the brain, liver, kidneys, and everything that needs a blood supply." Understanding how pannexin-1 regulates blood flow could lead to new treatments for multiple obesity-related conditions.

"Mark is a highly motivated postdoctoral researcher, and this award allows him to further scientific understanding of how obesity is linked with blood vessel spasms in patients' hearts," said Johnstone, an assistant professor at the Fralin Biomedical Research Institute. "He continues to be extremely productive, working with world-class researchers as he builds momentum toward his eventual goal of starting his own research group."

Renton also works closely with Professor Steven Poelzing and Assistant Professor Jessica Pfleger, both primary faculty in the institute's Center for Vascular and Heart Research.