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Researchers earn $2.2 million NIH grant to prevent development of AFib

Research by an interdisciplinary team of scientists from The Ohio State University could have a fundamental impact on future treatments for atrial fibrillation, the most common type of heart arrhythmia.

Led by Biomedical Engineering Assistant Professor Rengasayee (Sai) Rengasayee VeeraraghavanVeeraraghavanVeeraraghavan, the research team has received a $2.2 million five-year grant from the National Institutes of Health for their work to develop new techniques that could prevent the development and progression of atrial fibrillation.

Often called AFib or AF, atrial fibrillation is an irregular heartbeat that affects an estimated 2.7 to 6.1 million Americans, according to the Centers for Disease Control and Prevention. But existing therapies only focus on management of AF symptoms without addressing its underlying causes. Because it’s a progressive disease, it grows in severity over time and increases patients’ risk of serious complications like stroke and heart failure, said Veeraraghavan.

“Current treatments manage the symptoms of atrial fibrillation, but cannot reverse the disease process. By understanding the structural changes that underlie atrial fibrillation, we hope to fix the heart at the molecular level,” he said. “Our work could lead to unprecedented new treatments that prevent the development and progression of atrial fibrillation.”

microscopy image of intercalated disk nanodomainsAn image of intercalated disk nanodomains showing a transmission electron micrograph (left) and an image generated by Stochastic Optical Reconstruction Microscopy (STORM), which is a light microscopy technique that localizes individual protein molecules.

Using recently developed microscopy techniques, Veeraraghavan and his team are exploring how structures called intercalated disk nanodomains, which are 10,000 times smaller than the width of a strand of hair, coordinate the heartbeat. They are also discovering how leaky blood vessels can disrupt these structures, and thereby the heartbeat, leading to AF.

“Based on these insights, we are designing new treatments that will restore these tiny structures and prevent atrial fibrillation,” said Veeraraghavan.

Veeraraghavan’s co-investigators on the grant project are: Sandor Gyorke, professor in the Department of Physiology; Prez Radwanski, professor in the College of Pharmacy; Robert Williams, assistant director for research and development at the Center of Electron Microscopy and Analysis; and Brant Isakson, a professor of molecular physiology and biological physics at the University of Virginia.

a schematic of the project conceptFor a condition as intricate and complex as AF, an interdisciplinary team is key to addressing the issue, said Veeraraghavan, whose lab is located within Wexner Medical Center and allows for more seamless collaboration with colleagues.

“Atrial fibrillation has many dimensions,” he explained. “Which proteins are involved? How are they organized inside cells? How are blood vessels regulated? How do they influence heart muscle cells? Addressing such a wide range of questions requires a wide range of expertise.

“Being at an institution like Ohio State means that experts in such diverse areas are literally next door. This allows cross-training of the students and postdocs working on the project and gives them an interdisciplinary perspective from the earliest stages of their careers.”

This research is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health.

by Meggie Biss, College of Engineering Communications | biss.11@osu.edu