Ablation of phospholamban rescues reperfusion arrhythmias but exacerbates myocardium infarction in hearts with Ca2+/calmodulin kinase II constitutive phosphorylation of ryanodine receptors

Cardiovascular Research
Carlos A ValverdeAlicia Mattiazzi

Abstract

Abnormal Ca2+ release from the sarcoplasmic reticulum (SR), associated with Ca2+-calmodulin kinase II (CaMKII)-dependent phosphorylation of RyR2 at Ser2814, has consistently been linked to arrhythmogenesis and ischaemia/reperfusion (I/R)-induced cell death. In contrast, the role played by SR Ca2+ uptake under these stress conditions remains controversial. We tested the hypothesis that an increase in SR Ca2+ uptake is able to attenuate reperfusion arrhythmias and cardiac injury elicited by increased RyR2-Ser2814 phosphorylation. We used WT mice, which have been previously shown to exhibit a transient increase in RyR2-Ser2814 phosphorylation at the onset of reperfusion; mice with constitutive pseudo-phosphorylation of RyR2 at Ser2814 (S2814D) to exacerbate CaMKII-dependent reperfusion arrhythmias and cardiac damage, and phospholamban (PLN)-deficient-S2814D knock-in (SDKO) mice resulting from crossbreeding S2814D with phospholamban knockout deficient (PLNKO) mice. At baseline, S2814D and SDKO mice had structurally normal hearts. Moreover none of the strains were arrhythmic before ischaemia. Upon cardiac I/R, WT, and S2814D hearts exhibited abundant arrhythmias that were prevented by PLN ablation. In contrast, PLN ablation increase...Continue Reading

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Citations

Mar 11, 2020·Journal of Cellular and Molecular Medicine·Sean M DavidsonUNKNOWN EU-CARDIOPROTECTION COST Action (CA16225)
Sep 29, 2020·The Journal of General Physiology·Alejandra Cely-OrtizAlicia Mattiazzi
Mar 12, 2020·International Journal of Molecular Sciences·Natalia Jorgelina PradoEmiliano Raúl Diez
Apr 9, 2020·International Journal of Molecular Sciences·Bin LiuSándor Györke
Nov 9, 2019·Heart Failure Reviews·Liu ZhihaoFan Guanwei
Feb 19, 2021·Circulation Research·Alicia MattiazziEvangelia G Kranias
Jul 6, 2021·Journal of the American Heart Association·María Florencia RacioppiMartín Vila Petroff
Jan 4, 2022·Pflügers Archiv : European journal of physiology·Carolina Jaquenod De GiustiAlicia Mattiazzi
Jan 11, 2022·The Journal of Physiology·Carlos A Valverde, Alicia Mattiazzi

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