Tachy-paced cardiomyocyte-derived small extracellular vesicles impair SERCA2a-dependent Ca²⁺ handling in recipient cardiomyocytes.
- 1Department of Cardiovascular Medicine, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
- 2Department of Clinical and Diagnostic Laboratory Science, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Abstract
Background
Sustained tachyarrhythmia is a major cause of cardiac dysfunction and can lead to tachycardia-induced cardiomyopathy (TIC). However, the role of small extracellular vesicle (sEV)-mediated intercellular communication in the pathogenesis of TIC remains poorly understood. We aimed to investigate whether sEVs derived from tachy-paced cardiomyocytes affect intracellular Ca²⁺ handling in recipient cardiomyocytes.Methods and results
Cultured murine atrial cardiomyocytes (HL-1 cells) were subjected to high-frequency electrical stimulation (tachy-pacing, 10 Hz), and sEVs were isolated from the culture supernatant. sEVs derived from the tachy-paced cells and non-paced control cells were subsequently applied to neonatal mouse cardiomyocytes (NMCMs). Intracellular Ca²⁺ transients, sarcoplasmic reticulum (SR) Ca²⁺ content, and the expression of Ca²⁺-handling proteins were evaluated. High-frequency electrical stimulation significantly increased sEV secretion from HL-1 cells. sEVs derived from tachy-paced HL-1 cells markedly slowed Ca²⁺ decay and reduced SERCA2a protein expression in recipient NMCMs.Conclusions
Our study demonstrates that sEVs derived from tachy-paced cardiomyocytes suppress SERCA2a expression, thereby leading to impaired SR Ca²⁺ reuptake and prolonged Ca²⁺ transients. These findings suggest that sEV-mediated signaling may contribute to Ca²⁺ dysregulation during sustained tachycardia.
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BibTeX
@article{wei2026tachypaced,
title = {{Tachy-paced cardiomyocyte-derived small extracellular vesicles impair SERCA2a-dependent Ca²⁺ handling in recipient cardiomyocytes.}},
author = {Lai Wei and Satoshi Iwamiya and Kohei Kawajiri and Junji Yamaguchi and Minori Kurata and Kensuke Ihara and Tetsuo Sasano},
journal = {Journal of molecular and cellular cardiology plus},
year = {2026},
month = oct,
doi = {10.1016/j.jmccpl.2026.100874},
url = {https://europepmc.org/article/MED/42927336},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Tachy-paced cardiomyocyte-derived small extracellular vesicles impair SERCA2a-dependent Ca²⁺ handling in recipient cardiomyocytes.
AU - Lai Wei
AU - Satoshi Iwamiya
AU - Kohei Kawajiri
AU - Junji Yamaguchi
AU - Minori Kurata
AU - Kensuke Ihara
AU - Tetsuo Sasano
PY - 2026
DA - 2026/10/07
JO - Journal of molecular and cellular cardiology plus
DO - 10.1016/j.jmccpl.2026.100874
UR - https://europepmc.org/article/MED/42927336
AB - Background Sustained tachyarrhythmia is a major cause of cardiac dysfunction and can lead to tachycardia-induced cardiomyopathy (TIC). However, the role of small extracellular vesicle (sEV)-mediated intercellular communication in the pathogenesis of TIC remains poorly understood. We aimed to investigate whether sEVs derived from tachy-paced cardiomyocytes affect intracellular Ca²⁺ handling in recipient cardiomyocytes.Methods and results Cultured murine atrial cardiomyocytes (HL-1 cells) were subjected to high-frequency electrical stimulation (tachy-pacing, 10 Hz), and sEVs were isolated from the culture supernatant. sEVs derived from the tachy-paced cells and non-paced control cells were subsequently applied to neonatal mouse cardiomyocytes (NMCMs). Intracellular Ca²⁺ transients, sarcoplasmic reticulum (SR) Ca²⁺ content, and the expression of Ca²⁺-handling proteins were evaluated. High-frequency electrical stimulation significantly increased sEV secretion from HL-1 cells. sEVs derived from tachy-paced HL-1 cells markedly slowed Ca²⁺ decay and reduced SERCA2a protein expression in recipient NMCMs.Conclusions Our study demonstrates that sEVs derived from tachy-paced cardiomyocytes suppress SERCA2a expression, thereby leading to impaired SR Ca²⁺ reuptake and prolonged Ca²⁺ transients. These findings suggest that sEV-mediated signaling may contribute to Ca²⁺ dysregulation during sustained tachycardia.
SN - 2772-9761
ER -