Author + information
- Hector Chapoy,
- Yuriana Oropeza-Almazan,
- Ana Gutiérrez-Rodríguez and
- Gerardo Garcia-Rivas
Introduction: Mitochondrial Ca2+ overload is an essential factor in ischemia/reperfusion injury. Since hypothyroid rats (Hypo) are protected from ischemia reperfusion injury (IR), we tested the hypothesis that thyroid status alters mitochondrial Ca2+ handling reducing mitochondrial Ca2+ overload and protects to permeability transition.
Methods: Male Wistar rats were divided into 2 groups: a control and group treated with 6-propyl-2-thiouracil (PTU) Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (0.05% w/v) to induce hypothyroidism. MCU expression was measured by qRT-PCR and western blot analysis. Using cardiac mitochondria from Hypo and control rats, we measured mitochondrial Ca2+ transport, membrane potential (ΔΨ) and permeability transition through Ca2+ retention capacity (CRC) by fluorometric assays. Isolated perfused hearts from Hypo and control rats were subjected to I/R. Hemodynamic parameters, infarct size, enzymatic biomarkers were measured.
Results: After PTU treatment, the thyroid hormones T3 and T4 levels showed a reduction of 50 and 45%, respectively. Mitochondrial Ca2+ uptake was significantly lower in Hypo than control mitochondria using succinate as substrate. CRC showed that mitochondria from Hypo rats were less prone to permeability transition in 50% respect to control. While there were no significant differences at resting ΔΨ, after Ca2+ addition 80% of Hypo mitochondria was able to recover from Ca2+ induced depolarization compared to 33% of control animals. Remarkably, mitochondrial Ca2+ uniporter (MCU) expression was 30% lower in mitochondria from Hypo versus control animals. Recovery of post-ischemic LVDP and ±dp/dt were lower in controls than that Hypo rats accordingly with permeability transition pore opening reduction in Hypo rats.
Conclusions: Our results suggest that mitochondria from hypothyroid rats have lower mitochondrial Ca2+ uptake and are able to maintain ΔΨ under conditions of Ca2+ overload. These differences are consistent with modulation of the MCU expression and activity and might be a mechanism by which hypothyroid heart is protected to ischemia/reperfusion injury.
Poster Hall, Hall C
Friday, March 17, 2017, 3:45 p.m.-4:30 p.m.
Session Title: Diabetes and Endothelial Dysfucntion in Heart Failure
Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic
Presentation Number: 1162-247
- 2017 American College of Cardiology Foundation