Underlying mechanism of the contractile dysfunction in atrophied ventricular myocytes from a murine model of hypothyroidism

Cell Calcium
Dolores MontalvoJulio Altamirano

Abstract

Hypothyroidism (Hypo) is a risk factor for cardiovascular diseases, including heart failure. Hypo rapidly induces Ca2+ mishandling and contractile dysfunction (CD), as well as atrophy and ventricular myocytes (VM) remodeling. Hypo decreases SERCA-to-phospholamban ratio (SERCA/PLB), and thereby contributes to CD. Nevertheless, detailed spatial and temporal Ca2+ cycling characterization in VM is missing, and contribution of other structural and functional changes to the mechanism underlying Ca2+ mishandling and CD, as transverse tubules (T-T) remodeling, mitochondrial density (Dmit) and energy availability, is unclear. Therefore, in a rat model of Hypo, we aimed to characterize systolic and diastolic Ca2+ signaling, T-T remodeling, Dmit, citrate synthase (CS) activity and high-energy phosphate metabolites (ATP and phosphocreatine). We confirmed a decrease in SERCA/PLB (59%), which slowed SERCA activity (48%), reduced SR Ca2+ (19%) and blunted Ca2+ transient amplitude (41%). Moreover, assessing the rate of SR Ca2+ release (dRel/dt), we found that early and maximum dRel/dt decreased, and this correlated with staggered Ca2+ transients. However, dRel/dt persisted during Ca2+ transient relaxation due to abundant late Ca2+ sparks. Isop...Continue Reading

Citations

Jun 11, 2019·Progress in Transplantation : Official Publication, North American Transplant Coordinators Organization ... [et Al.]·Anne Julie FrenetteKarim Serri
Aug 29, 2019·Thyroid : Official Journal of the American Thyroid Association·Héctor Chapoy-VillanuevaGerardo García-Rivas
Sep 10, 2019·Journal of Cardiovascular Pharmacology and Therapeutics·María Inés RagoneAlicia E Consolini
Jan 31, 2020·Circulation Research·David A EisnerDavid C Hutchings
Feb 16, 2019·Journal of Molecular and Cellular Cardiology·Rachel A MinerathChad E Grueter
Jun 28, 2021·Journal of Molecular and Cellular Cardiology·Nimra GilaniKaie Ojamaa

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