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- W2091416904 abstract "Higher risk of developing life threatening cardiac arrhythmias, such as atrial fibrillation (AF) has been found in type 2 diabetes mellitus (T2DM), but the mechanism underlying the association is largely unknown. Our previous studies showed that circulating IgGs from certain advanced T2DM patients displayed anti-endothelial effects and often induced intracellular Ca release in endothelial cells. The present study is to test the hypothesis that circulating IgGs from T2DM patients with AF perturb intracellular Ca homeostasis in atrial cardiomyocytes which in turn trigger AF. Protein A-purified IgGs were obtained from a cohort of T2DM subjects with AF and subjects without AF or other cardiovascular complications. The data show that IgG (1 µg/mL) from T2DM AF patients caused acute intracellular Ca release in cultured mouse atrial cardiomyocytes HL-1 cells compared to control groups (p < 0.001). The IgG-mediated Ca release was insensitive to verapamil (20 µM), mibefradil (25 µM) or BTP-2 (5 µM), indicating that the Ca release is not through voltage-gated Ca channels or store-operated Ca entry. On the other hand, application of Xestospongin C (10 µM) or 2-APB (100 µM), two membrane-permeable IP3 receptor antagonists, or knockdown of IP3 receptor, significantly decreased Ca release stimulated by the IgGs from T2DM AF patients (p < 0.01). Taken together, our data suggest that circulating IgGs alter intracellular Ca homeostasis in cardiomyocytes through IP3 pathway in T2DM AF patients. Our studies may provide the mechanistic understanding on a causal role of circulating IgGs in T2DM patients with AF and other symptomatic cardiac conduction diseases. The IgGs may serve as a biomarker for identifying a subset of T2DM patients with increased risk for development of AF." @default.
- W2091416904 created "2016-06-24" @default.
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- W2091416904 date "2015-01-01" @default.
- W2091416904 modified "2023-09-25" @default.
- W2091416904 title "Purified IgGs from Type 2 Diabetes with Atrial Fibrillation Induce Intracellular Calcium Release in Cardiomyocytes through IP3 Pathway" @default.
- W2091416904 doi "https://doi.org/10.1016/j.bpj.2014.11.604" @default.
- W2091416904 hasPublicationYear "2015" @default.
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