Alterations of sarcoplasmic reticulum-mediated Ca 2+ uptake in a model of premature ventricular contraction (PVC)-induced cardiomyopathy.

Autor: Balderas-Villalobos J; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, 1101 E Marshall St, 3-038H, Richmond, VA, 23298, USA., Medina-Contreras JML; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, 1101 E Marshall St, 3-038H, Richmond, VA, 23298, USA., Lynch C; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, 1101 E Marshall St, 3-038H, Richmond, VA, 23298, USA., Kabadi R; Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA., Ramirez RJ; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, 1101 E Marshall St, 3-038H, Richmond, VA, 23298, USA., Tan AY; Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.; Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA., Kaszala K; Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.; Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA., Samsó M; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, 1101 E Marshall St, 3-038H, Richmond, VA, 23298, USA., Huizar JF; Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.; Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA., Eltit JM; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, 1101 E Marshall St, 3-038H, Richmond, VA, 23298, USA. jose.eltit@vcuhealth.org.
Jazyk: angličtina
Zdroj: Molecular and cellular biochemistry [Mol Cell Biochem] 2023 Jul; Vol. 478 (7), pp. 1447-1456. Date of Electronic Publication: 2022 Nov 09.
DOI: 10.1007/s11010-022-04605-y
Abstrakt: Premature ventricular contractions (PVCs) are the most frequent ventricular arrhythmias in the overall population. PVCs are known to acutely enhance contractility by the post-extrasystolic potentiation phenomenon, but over time persistent PVCs promote PVC-induced cardiomyopathy (PVC-CM), characterized by a reduction of the left ventricular (LV) ejection fraction. Ca 2+ cycling in myocytes commands muscle contraction and in this process, SERCA2 leads the Ca 2+ reuptake into the sarcoplasmic reticulum (SR) shaping cytosolic Ca 2+ signal decay and muscle relaxation. Altered Ca 2+ reuptake can contribute to the contractile dysfunction observed in PVC-CM. To better understand Ca 2+ handling using our PVC-CM model (canines with 50% PVC burden for 12 weeks), SR-Ca 2+ reuptake was investigated by measuring Ca 2+ dynamics and analyzing protein expression. Kinetic analysis of Ca 2+ reuptake in electrically paced myocytes showed a ~ 21 ms delay in PVC-CM compared to Sham in intact isolated myocytes, along with a ~ 13% reduction in SERCA2 activity assessed in permeabilized myocytes. Although these trends were not statistically significant between groups using hierarchical statistics, relaxation of myocytes following contraction was significantly slower in PVC-CM vs Sham myocytes. Western blot analyses indicate a 22% reduction in SERCA2 expression, a 23% increase in phospholamban (PLN) expression, and a 50% reduction in PLN phosphorylation in PVC-CM samples vs Sham. Computational analysis simulating a 20% decrease in SR-Ca 2+ reuptake resulted in a ~ 22 ms delay in Ca 2+ signal decay, consistent with the experimental result described above. In conclusion, SERCA2 and PLB alterations described above have a modest contribution to functional adaptations observed in PVC-CM.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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