文章基本信息

标题：Circulating IgGs in Type 2 Diabetes with Atrial Fibrillation Induce IP 3-Mediated Calcium Elevation in Cardiomyocytes
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作者：Yanhong Luo ; Xian Liu ; Ruilian Ma 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：4
页码：1-15
DOI：10.1016/j.isci.2020.101036
语种：English
出版社：Elsevier
摘要：SummaryHigher risk of cardiac arrhythmias including atrial fibrillation (AF) associates with type 2 diabetes mellitus (T2DM) with the underlying mechanism largely unknown. The present study reported a subset of circulating immunoglobulin G autoantibodies (IgGs) from patients with T2DM with AF (T2DM/AF)-induced intracellular calcium elevation in both human induced pluripotent stem cell (iPSC)-derived and mouse atrial cardiomyocytes, whereas (identical concentrations of) IgGs from patients with T2DM without AF could not. The IgG-evoked intracellular calcium elevation was insensitive to verapamil, mibefradil, or BTP-2, indicating calcium source from neither voltage-gated calcium channels nor store-operated calcium entry. On the other hand, pharmacological antagonism or genetic knockdown of inositol triphosphate (IP3) receptor significantly decreased T2DM/AF IgG-induced intracellular calcium elevation. Furthermore, pharmacological blockage of G protein-coupled receptor (GPCR), heterotrimeric G protein or phospholipase C dampened IgG-induced intracellular calcium elevation. Taken together, circulating IgGs from patients with T2DM/AF stimulated arrhythmogenic intracellular calcium elevation through IP3pathway in atrial cardiomyocytes.Graphical AbstractDisplay OmittedHighlights•Identification of cardiomyocyte-targeting IgGs in T2DM atrial fibrillation patients•Induction of arrhythmogenic Ca2+signaling by these IgGs•Independent of voltage-gated or store-operated Ca2+channels•Involvement of GPCR-IP3-IP3R axis in IgG-evoked intracellular Ca2+elevationBiological Sciences; Physiology; Pathophysiology; Cellular Physiology