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Lab Uncovers Role of Metabolic Signaling in Preventing Atrial Fibrillation

April 22, 2022
by Elisabeth Reitman

Research from the Yale School of Medicine indicates that a protein kinase that is a master regulator of cell metabolism is critical to preventing atrial fibrillation. The research appeared April 22 in the journal JCI Insight.

Lawrence H. Young, MD, professor of medicine and cellular and molecular physiology, and senior author of the study, said that the link between metabolic stress and atrial fibrillation is not well-understood.

“We need to understand the mechanisms linking metabolic disease and the genesis of atrial fibrillation,” said Young. "Our aim was to define the role of AMPK in preventing atrial molecular, electrophysiological, and structural remodeling.”

The research team used genetically altered mice to explore the biological effects of the enzyme AMP-activated protein kinase (AMPK) in the atria, the upper chambers of the heart. AMPK is essential to maintaining metabolic function in the heart and other organs. In collaboration with Fadi G. Akar, PhD, an associate professor who co-authored the study, the Young lab demonstrated the adverse impact of genetic deletion of AMPK on atrial molecular, electrical, and structural remodeling culminating in persistent atrial fibrillation.

The authors also found that Pitx2c and Mef2c — transcription factors that are essential in cardiac development — are affected by AMPK deletion and are critical in maintaining normal atrial molecular programing.

While additional research is needed, the findings suggest that reduced AMPK activity that occurs in elderly patients with metabolic disease, such as diabetes and obesity, might contribute to atrial enlargement and the development of electrical dysfunction. The discovery could lead to potential therapies for atrial fibrillation that address the underlying cause of the disease.

Atrial fibrillation is the most common arrhythmia, or heart rhythm disturbance. The incidence of atrial fibrillation is rising, and these arrhythmias are known to cause blood clots, stroke, heart failure, and other cardiovascular complications.

Yale’s Kevin N. Su, Yina Ma, Marine Cacheux, Grace K. Muller, Xiaohong Wu, Nicole Guerrera, Stephanie L. Thorn, Albert J. Sinusas, Joseph G. Akar, and Fadi G. Akar contributed to the study. Other coauthors are Zeki Ilkan and Nour Raad from the Icahn School of Medicine at Mount Sinai; Marc Foretz and Benoit Viollet from the University of Paris.

Submitted by Elisabeth Reitman on April 22, 2022