ISSN 2149-2263 | E-ISSN 2149-2271
The Anatolian Journal of Cardiology
Hypoxia-Induced Sarcoplasmic Reticulum Ca2+ Leak Is Reversed by Ryanodine Receptor Stabilizer JTV-519 in HL-1 Cardiomyocytes [Anatol J Cardiol]
Anatol J Cardiol. 2022; 26(6): 476-484 | DOI: 10.5152/AnatolJCardiol.2022.1223

Hypoxia-Induced Sarcoplasmic Reticulum Ca2+ Leak Is Reversed by Ryanodine Receptor Stabilizer JTV-519 in HL-1 Cardiomyocytes

Minh Duc Trinh1, Ivana Fišerová1, Lukáš Vacek1, Marek Heide1, Jan Pala1, Petr Tousek2, Jan Polak1
1Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
2Department of Cardiology, University Hospital Královské Vinohrady, Prague, Czech Republic
3Department of Internal Medicine, University Hospital Královské Vinohrady, Prague, Czech Republic

Background: To assess whether hypoxia, as can be found in obstructive sleep apnea syndrome, is causally associated with the development of heart failure through a direct effect on calcium leakage from the sarcoplasmic reticulum.

Methods: The impact of hypoxia on sarcoplasmic reticulum calcium leakage and expression of RyR2 (ryanodine receptor2) and SERC2a (sarcoplasmic reticulum Ca2+ATPase 2a) was investigated together with the outcomes of JTV-519 and S107 treatment. HL-1 cardiomyocytes were cultured for 7 days on gas-permeable cultureware under control (12% O2) or hypoxic (1% O2) conditions with or without JTV-519 or S107. SRCL was assessed using a Fluo-5N probe. Gene and protein expression was analyzed using qPCR and western blotting.

Results: Hypoxic exposure increased sarcoplasmic reticulum calcium leakage by 39% and reduced RyR2 gene expression by 52%. No effect on RyR2 protein expression was observed. Treatment with 1µM JTV-519 reduced sarcoplasmic reticulum calcium leakage by 52% and 35% under control and hypoxic conditions, respectively. Administration of 1 µM JTV-519 increased RyR2 gene expression by 89% in control conditions. No effect on SRCL, RyR2, or SERC2a gene, or protein expression was observed with S107 treatment.

Conclusion: Hypoxia increased sarcoplasmic reticulum calcium leakage which was ameliorated by JTV-519 treatment independently of gene or protein expression. JTV-519 rep-resents a possible treatment for obstructive sleep apnea-associated HF.

Keywords: Calcium, heart failure, obstructive sleep apnea, hypoxia, ryanodine receptor

Minh Duc Trinh, Ivana Fišerová, Lukáš Vacek, Marek Heide, Jan Pala, Petr Tousek, Jan Polak. Hypoxia-Induced Sarcoplasmic Reticulum Ca2+ Leak Is Reversed by Ryanodine Receptor Stabilizer JTV-519 in HL-1 Cardiomyocytes. Anatol J Cardiol. 2022; 26(6): 476-484

Corresponding Author: Minh Duc Trinh
Manuscript Language: English


Journal Metrics

Journal Citation Indicator: 0.18
CiteScore: 1.1
Source Normalized Impact
per Paper:
0.22
SCImago Journal Rank: 0.348

Quick Search



Copyright © 2024 The Anatolian Journal of Cardiology



Kare Publishing is a subsidiary of Kare Media.