PMID- 32315831
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210110
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 23
IP  - 4
DP  - 2020 Apr 24
TI  - Circulating IgGs in Type 2 Diabetes with Atrial Fibrillation Induce 
      IP(3)-Mediated Calcium Elevation in Cardiomyocytes.
PG  - 101036
LID - S2589-0042(20)30220-0 [pii]
LID - 10.1016/j.isci.2020.101036 [doi]
LID - 101036
AB  - 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.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Luo, Yanhong
AU  - Luo Y
AD  - Davis Heart and Lung Research Institute, Ohio State University-Wexner Medical 
      Center, Columbus, OH 43210, USA; Department of Endocrinology, The Children's 
      Hospital of Chongqing Medical University, Chongqing, P. R. China.
FAU - Liu, Xian
AU  - Liu X
AD  - Department of Kinesiology, University of Texas at Arlington, Arlington, TX 76010, 
      USA; College of Nursing and Health Innovation, University of Texas at Arlington, 
      Arlington, TX 76010, USA.
FAU - Ma, Ruilian
AU  - Ma R
AD  - Division of Regenerative Medicine Research, Department of Pathology and 
      Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45219, USA.
FAU - Wang, Yigang
AU  - Wang Y
AD  - Division of Regenerative Medicine Research, Department of Pathology and 
      Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45219, USA.
FAU - Zimering, Mark
AU  - Zimering M
AD  - Endocrinology, Veterans Affairs New Jersey Healthcare System, East Orange, NJ 
      07018, USA; Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, 
      USA. Electronic address: mark.zimering@va.gov.
FAU - Pan, Zui
AU  - Pan Z
AD  - Davis Heart and Lung Research Institute, Ohio State University-Wexner Medical 
      Center, Columbus, OH 43210, USA; Department of Kinesiology, University of Texas 
      at Arlington, Arlington, TX 76010, USA; College of Nursing and Health Innovation, 
      University of Texas at Arlington, Arlington, TX 76010, USA. Electronic address: 
      zui.pan@uta.edu.
LA  - eng
PT  - Journal Article
DEP - 20200408
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC7170991
OTO - NOTNLM
OT  - Biological Sciences
OT  - Cellular Physiology
OT  - Pathophysiology
OT  - Physiology
COIS- Declaration of Interests The authors declare no competing interests. The contents 
      do not represent the views of the U.S. Department of Veteran Affairs or the 
      United States government.
EDAT- 2020/04/22 06:00
MHDA- 2020/04/22 06:01
PMCR- 2020/04/08
CRDT- 2020/04/22 06:00
PHST- 2019/08/30 00:00 [received]
PHST- 2020/01/16 00:00 [revised]
PHST- 2020/04/01 00:00 [accepted]
PHST- 2020/04/22 06:00 [pubmed]
PHST- 2020/04/22 06:01 [medline]
PHST- 2020/04/22 06:00 [entrez]
PHST- 2020/04/08 00:00 [pmc-release]
AID - S2589-0042(20)30220-0 [pii]
AID - 101036 [pii]
AID - 10.1016/j.isci.2020.101036 [doi]
PST - ppublish
SO  - iScience. 2020 Apr 24;23(4):101036. doi: 10.1016/j.isci.2020.101036. Epub 2020 
      Apr 8.