Atrial fibrillation complicated by heart failure induces distinct remodeling of calcium cycling proteins

PloS One
Patrick LugenbielDierk Thomas

Abstract

Atrial fibrillation (AF) and heart failure (HF) are two of the most common cardiovascular diseases. They often coexist and account for significant morbidity and mortality. Alterations in cellular Ca2+ homeostasis play a critical role in AF initiation and maintenance. This study was designed to specifically elucidate AF-associated remodeling of atrial Ca2+ cycling in the presence of mild HF. AF was induced in domestic pigs by atrial burst pacing. The animals underwent electrophysiologic and echocardiographic examinations. Ca2+ handling proteins were analyzed in right atrial tissue obtained from pigs with AF (day 7; n = 5) and compared to sinus rhythm (SR) controls (n = 5). During AF, animals exhibited reduction of left ventricular ejection fraction (from 73% to 58%) and prolonged atrial refractory periods. AF and HF were associated with suppression of protein kinase A (PKA)RII (-62%) and Ca2+-calmodulin-dependent kinase II (CaMKII) δ by 37%, without changes in CaMKIIδ autophosphorylation. We further detected downregulation of L-type calcium channel (LTCC) subunit α2 (-75%), sarcoplasmic reticulum Ca2+-ATPase (Serca) 2a (-29%), phosphorylated phospholamban (Ser16, -92%; Thr17, -70%), and phospho-ryanodine receptor 2 (RyR2) (Ser28...Continue Reading

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Citations

Sep 1, 2015·Frontiers in Pharmacology·Alex S JohnstonJoseph R Burgoyne
Jan 13, 2017·Journal of Molecular and Cellular Cardiology·Jordi HeijmanDobromir Dobrev
Oct 12, 2017·Circulation. Arrhythmia and Electrophysiology·Jonas Goldin DinessBo Hjorth Bentzen
Oct 4, 2016·American Journal of Physiology. Heart and Circulatory Physiology·F HohendannerL A Blatter
Jul 19, 2018·Biophysics Reviews·Ann-Kathrin RahmDierk Thomas
Jul 28, 2020·Circulation Research·Dominik SchüttlerWilliam J Hucker
Mar 22, 2019·ELife·Wenli DaiChristopher R Weber
Oct 20, 2018·Frontiers in Physiology·Nathan C DenhamKatharine M Dibb
Mar 22, 2019·Nature Reviews. Cardiology·Sebastian ClaussStefan Kääb
Feb 17, 2021·Pflügers Archiv : European journal of physiology·Charia McKeeXun Ai
May 29, 2021·Pharmacogenomics and Personalized Medicine·Ann-Kathrin RahmDierk Thomas

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Methods Mentioned

BETA
electrophoresis
protein assay

Software Mentioned

ImageJ
EP

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