TY - JOUR
T1 - Mitochondrial Ca2+ Uniporter–Dependent Energetic Dysfunction Drives Hypertrophy in Heart Failure
AU - Alves-Figueiredo, Hugo
AU - Silva-Platas, Christian
AU - Estrada, Manuel
AU - Oropeza-Almazán, Yuriana
AU - Ramos-González, Martin
AU - Bernal-Ramírez, Judith
AU - Vázquez-Garza, Eduardo
AU - Tellez, Armando
AU - Salazar-Ramírez, Felipe
AU - Méndez-Fernández, Abraham
AU - Galaz, José Luis
AU - Lobos, Pedro
AU - Youker, Keith
AU - Lozano, Omar
AU - Torre-Amione, Guillermo
AU - García-Rivas, Gerardo
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/4
Y1 - 2024/4
N2 - The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)–induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B–dependent hypertrophic and proinflammatory signaling. Moreover, we identified a calcium/calmodulin–independent protein kinase II/cyclic adenosine monophosphate response element–binding protein signaling modulating MCU upregulation by ANGII. Additionally, we found upregulation of MCU in ANGII-induced left ventricular HF in mice, and in the LV of HF patients, which was correlated with pathological remodeling. Following left ventricular assist device implantation, MCU expression decreased, suggesting tissue plasticity to modulate MCU expression.
AB - The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)–induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B–dependent hypertrophic and proinflammatory signaling. Moreover, we identified a calcium/calmodulin–independent protein kinase II/cyclic adenosine monophosphate response element–binding protein signaling modulating MCU upregulation by ANGII. Additionally, we found upregulation of MCU in ANGII-induced left ventricular HF in mice, and in the LV of HF patients, which was correlated with pathological remodeling. Following left ventricular assist device implantation, MCU expression decreased, suggesting tissue plasticity to modulate MCU expression.
KW - heart failure
KW - mitochondrial calcium overload
KW - mitochondrial calcium uniporter
KW - mitochondrial dysfunction
KW - pathological remodeling
KW - reactive oxygen species
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U2 - 10.1016/j.jacbts.2024.01.007
DO - 10.1016/j.jacbts.2024.01.007
M3 - Article
AN - SCOPUS:85189972713
SN - 2452-302X
VL - 9
SP - 496
EP - 518
JO - JACC: Basic to Translational Science
JF - JACC: Basic to Translational Science
IS - 4
ER -