scholarly journals Cardiac overexpression of perilipin 2 induces atrial steatosis, connexin 43 remodeling, and atrial fibrillation in aged mice

2019 ◽  
Vol 317 (6) ◽  
pp. E1193-E1204 ◽  
Author(s):  
Satsuki Sato ◽  
Jinya Suzuki ◽  
Masamichi Hirose ◽  
Mika Yamada ◽  
Yasuo Zenimaru ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Connexin 43 ◽  
Hormone Sensitive Lipase ◽  
Mapping Technique ◽  
Lateral Side ◽  
Aged Mice ◽  
Obesity And Diabetes ◽  
Junction Protein ◽  
Cardiac Steatosis ◽  
Perilipin 2

Atrial fibrillation (AF) is prevalent in patients with obesity and diabetes, and such patients often exhibit cardiac steatosis. Since the role of cardiac steatosis per se in the induction of AF has not been elucidated, the present study was designed to explore the relation between cardiac steatosis and AF. Transgenic (Tg) mice with cardiac-specific overexpression of perilipin 2 (PLIN2) were housed in the laboratory for more than 12 mo before the study. Electron microscopy of the atria of PLIN2-Tg mice showed accumulation of small lipid droplets around mitochondrial chains, and five- to ninefold greater atrial triacylglycerol (TAG) content compared with wild-type (WT) mice. Electrocardiography showed significantly longer RR intervals in PLIN2-Tg mice than in WT mice. Transesophageal electrical burst pacing resulted in significantly higher prevalence of sustained (>5 min) AF (69%) in PLIN2-Tg mice than in WT mice (24%), although it was comparable in younger (4-mo-old) mice. Connexin 43 (Cx43), a gap junction protein, was localized at the intercalated disks in WT atria but was heterogeneously distributed on the lateral side of cardiomyocytes in PLIN2-Tg atria. Langendorff-perfused hearts using the optical mapping technique showed slower and heterogeneous impulse propagation in PLIN2-Tg atria compared with WT atria. Cardiac overexpression of hormone-sensitive lipase in PLIN2-Tg mice resulted in atrial TAG depletion and amelioration of AF susceptibility. The results suggest that PLIN2-induced steatosis is associated with Cx43 remodeling, impaired conduction propagation, and higher incidence of AF in aged mice. Therapies targeting cardiac steatosis could be potentially beneficial against AF in patients with obesity or diabetes.

Overexpression of Perilipin 2 Induces Cardiac Steatosis and Atrial Fibrillation via Connexin 43 Remodeling

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1903-P ◽  
Author(s):  
SATSUKI SATO ◽  
JINYA SUZUKI ◽  
MASAMICHI HIROSE ◽  
TAKAHIRO NAKAYA ◽  
MIKA YAMADA ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Connexin 43 ◽  
Cardiac Steatosis ◽  
Perilipin 2

Body Mass Index can influence Connexin 43 distribution in patients with atrial fibrillation or sinus rhythm

2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
S. Dhein ◽  
S. Rothe ◽  
A. Busch ◽  
H. Bittner ◽  
M. Kostelka ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Mass Index ◽  
Sinus Rhythm ◽  
Body Mass ◽  
Connexin 43

Phosphorylation of connexin 43 induced by traumatic brain injury promotes exosome release

2018 ◽  
Vol 119 (1) ◽  
pp. 305-311 ◽  
Author(s):  
Wei Chen ◽  
Yijun Guo ◽  
Wenjin Yang ◽  
Lei Chen ◽  
Dabin Ren ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gap Junction ◽  
Connexin 43 ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Cx43 Expression ◽  
Term Potentiation ◽  
Junction Protein

Traumatic brain injury (TBI) caused by the external force leads to the neuronal dysfunction and even death. TBI has been reported to significantly increase the phosphorylation of glial gap junction protein connexin 43 (Cx43), which in turn propagates damages into surrounding brain tissues. However, the neuroprotective and anti-apoptosis effects of glia-derived exosomes have also been implicated in recent studies. Therefore, we detected whether TBI-induced phosphorylation of Cx43 would promote exosome release in rat brain. To generate TBI model, adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury. Phosphorylated Cx43 protein levels and exosome activities were quantified using Western blot analysis following TBI. Long-term potentiation (LTP) was also tested in rat hippocampal slices. TBI significantly increased the phosphorylated Cx43 and exosome markers expression in rat ipsilateral hippocampus, but not cortex. Blocking the activity of Cx43 or ERK, but not JNK, significantly suppressed TBI-induced exosome release in hippocampus. Furthermore, TBI significantly inhibited the induction of LTP in hippocampal slices, which could be partially but significantly restored by pretreatment with exosomes. The results imply that TBI-activated Cx43 could mediate a nociceptive effect by propagating the brain damages, as well as a neuroprotective effect by promoting exosome release. NEW & NOTEWORTHY We have demonstrated in rat traumatic brain injury (TBI) models that both phosphorylated connexin 43 (p-Cx43) expression and exosome release were elevated in the hippocampus following TBI. The promoted exosome release depends on the phosphorylation of Cx43 and requires ERK signaling activation. Exosome treatment could partially restore the attenuated long-term potentiation. Our results provide new insight for future therapeutic direction on the functional recovery of TBI by promoting p-Cx43-dependent exosome release but limiting the gap junction-mediated bystander effect.

scholarly journals Sample Entropy Analysis of Noisy Atrial Electrograms during Atrial Fibrillation

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Eva María Cirugeda-Roldán ◽  
Antonio Molina Picó ◽  
Daniel Novák ◽  
David Cuesta-Frau ◽  
Vaclav Kremen
Keyword(s):  
Atrial Fibrillation ◽  
Heart Rhythm ◽  
Heart Tissue ◽  
Sample Entropy ◽  
Mapping Technique ◽  
Atrial Electrograms ◽  
Invasive Method ◽  
Atrial Electrogram ◽  
Focal Atrial Tachycardia ◽  
Class Segmentation

Most cardiac arrhythmias can be classified as atrial flutter, focal atrial tachycardia, or atrial fibrillation. They have been usually treated using drugs, but catheter ablation has proven more effective. This is an invasive method devised to destroy the heart tissue that disturbs correct heart rhythm. In order to accurately localise the focus of this disturbance, the acquisition and processing of atrial electrograms form the usual mapping technique. They can be single potentials, double potentials, or complex fractionated atrial electrogram (CFAE) potentials, and last ones are the most effective targets for ablation. The electrophysiological substrate is then localised by a suitable signal processing method. Sample Entropy is a statistic scarcely applied to electrograms but can arguably become a powerful tool to analyse these time series, supported by its results in other similar biomedical applications. However, the lack of an analysis of its dependence on the perturbations usually found in electrogram data, such as missing samples or spikes, is even more marked. This paper applied SampEn to the segmentation between non-CFAE and CFAE records and assessed its class segmentation power loss at different levels of these perturbations. The results confirmed that SampEn was able to significantly distinguish between non-CFAE and CFAE records, even under very unfavourable conditions, such as 50% of missing data or 10% of spikes.

Subcellular localization of the Na+/H+ exchanger NHE1 in rat myocardium

1999 ◽  
Vol 276 (2) ◽  
pp. H709-H717 ◽  
Author(s):  
Kevin Petrecca ◽  
Roxana Atanasiu ◽  
Sergio Grinstein ◽  
John Orlowski ◽  
Alvin Shrier
Keyword(s):  
Connexin 43 ◽  
Cell Types ◽  
Ph Homeostasis ◽  
Adult Rat ◽  
Junction Protein ◽  
Close Proximity ◽  
Gap Junction Protein ◽  
Intercalated Disks ◽  
Distinct Distribution ◽  
Intercalated Disk

The Na+/H+exchanger NHE1 isoform is an integral component of cardiac intracellular pH homeostasis that is critically important for myocardial contractility. To gain further insight into its physiological significance, we determined its cellular distribution in adult rat heart by using immunohistochemistry and confocal microscopy. NHE1 was localized predominantly at the intercalated disk regions in close proximity to the gap junction protein connexin 43 of atrial and ventricular muscle cells. Significant labeling of NHE1 was also observed along the transverse tubular systems, but not the lateral sarcolemmal membranes, of both cell types. In contrast, the Na+-K+-ATPase α1-subunit was readily labeled by a specific mouse monoclonal antibody (McK1) along the entire ventricular sarcolemma and intercalated disks and, to a lesser extent, in the transverse tubules. These results indicate that NHE1 has a distinct distribution in heart and may fulfill specialized roles by selectively regulating the pH microenvironment of pH-sensitive proteins at the intercalated disks (e.g., connexin 43) and near the cytosolic surface of sarcoplasmic reticulum cisternae (e.g., ryanodine receptor), thereby influencing impulse conduction and excitation-contraction coupling.

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