%0 Journal Article
%T Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.
%A Cizauskas HE
%A Burnham HV
%A Panni A
%A Pena A
%A Alvarez-Arce A
%A Davis MT
%A Araujo K
%A Delligatti C
%A Edassery S
%A Kirk JA
%A Arora R
%A Barefield DY
%J Am J Physiol Heart Circ Physiol
%V 0
%N 0
%D 2024 Jun 28
%M 38940916
%F 5.125
%R 10.1152/ajpheart.00148.2024
%X Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance, often treated via electrical cardioversion. Following rhythm restoration, a period of depressed mechanical function known as atrial stunning occurs, suggesting that defects in contractility occur in AFib and are revealed upon restoration of rhythm. This project aims to define the contractile remodeling that occurs in AFib. To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared to sinus rhythm atria. Atrial cardiomyocytes showed reduced force of contraction, decreased resting tension, and increased calcium sensitivity in skinned single cardiomyocyte studies. These alterations correlated with degradation of myofilament proteins including myosin heavy chain altering force of contraction, titin altering resting tension, and TnI altering calcium sensitivity. We measured degradation of other myofilament proteins including cMyBP-C and actininshowing significant degradation in the AFib samples compared to sinus rhythm atria. Many of the protein degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. These results provide an understanding of the contractile remodeling that occurs in AFib and provide insight into the molecular explanation for atrial stunning and the increased risk of atrial thrombus and stroke in AFib.