April 11, 2022

Peptides promote AFib arrhythmia

Peptide oligomers have detrimental metabolic effects and cause pro-arrhythmic electrophysiological changes in heart atria, suggesting they may contribute to atrial fibrillation.

by Leigh MacMillan

Atrial fibrillation (AFib) — the most common cardiac arrhythmia worldwide — increases the risk of stroke, heart failure and other cardiac complications, and current treatments are ineffective for many patients. 

Aging is the most important risk factor for AFib. With aging, atria develop amyloid (protein aggregates) composed of the natriuretic peptides ANP and BNP. Katherine Murray, MD, and colleagues previously identified pre-amyloid oligomers of ANP in human atria associated with hypertension and in a mouse model of AFib. 

They have now probed the effects of oligomers derived from ANP, BNP and a mutant ANP that is associated with an inherited form of AFib. They found that the oligomers (but not monomers) had detrimental metabolic effects and caused pro-arrhythmic electrophysiological changes in atrial cells and hypertensive mice. 

The studies, reported in Circulation: Arrhythmia and Electrophysiology, point to natriuretic peptide oligomers as pro-arrhythmia mediators in the atria and support a causative role for mutant ANP in the pathophysiology of the associated inherited AFib.

Zhenjiang Yang, MD, PhD, and Tuerdi Subati, MD, PhD, are co-first authors of the recent paper. Other authors include Kyungsoo Kim, PhD, Matthew Murphy, PharmD, Owen Dougherty, Isis Christopher, Joseph Van Amburg, Kaylen Woodall, and Joey Barnett, PhD. The research was supported by the National Institutes of Health (grants HL096844, HL133127, TR000445) and American Heart Association.