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Circulating IgGs in Type 2 Diabetes with Atrial Fibrillation Induce IP3-Mediated Calcium Elevation in Cardiomyocytes

Year: 2020

Type: article

Abstract: Higher 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 (IP 3 ) 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 IP 3 pathway in atrial cardiomyocytes.

Source: iScience

DOI: 10.1016/j.isci.2020.101036

Authors: Yanhong Luo, Xian Liu, Ruilian Ma, Yigang Wang, Mark Zimering, Zui Pan