Guitart-Mampel 2018 Biochim Biophys Acta
|Guitart-Mampel M, Gonzalez-Tendero A, Niñerola S, Morén C, Catalán-Garcia M, González-Casacuberta I, Juárez-Flores DL, Ugarteburu O, Matalonga L, Cascajo MV, Tort F, Cortés A, Tobias E, Milisenda JC, Grau JM, Crispi F, Gratacós E, Garrabou G, Cardellach F (2018) Cardiac and placental mitochondrial characterization in a rabbit model of intrauterine growth restriction. Biochim Biophys Acta 1862:1157-67.|
Guitart-Mampel M, Gonzalez-Tendero A, Ninerola S, Moren C, Catalan-Garcia M, Gonzalez-Casacuberta I, Juarez-Flores DL, Ugarteburu O, Matalonga L, Cascajo MV, Tort F, Cortes A, Tobias E, Milisenda JC, Grau JM, Crispi F, Gratacos E, Garrabou G, Cardellach F (2018) Biochim Biophys Acta
Abstract: Intrauterine growth restriction (IUGR) is associated with cardiovascular remodeling persisting into adulthood. Mitochondrial bioenergetics, essential for embryonic development and cardiovascular function, are regulated by nuclear effectors as sirtuins. A rabbit model of IUGR and cardiovascular remodeling was generated, in which heart mitochondrial alterations were observed by microscopic and transcriptomic analysis. We aimed to evaluate if such alterations are translated at a functional mitochondrial level to establish the etiopathology and potential therapeutic targets for this obstetric complication.
Hearts and placentas from 16 IUGR-offspring and 14 controls were included to characterize mitochondrial function.
Enzymatic activities of complexes II, IV and II + III in IUGR-hearts (-11.96 ± 3.16%; -15.58 ± 5.32%; -14.73 ± 4.37%; p < 0.05) and II and II + III in IUGR-placentas (-17.22 ± 3.46%; p < 0.005 and -29.64 ± 4.43%; p < 0.001) significantly decreased. This was accompanied by a not significant reduction in CI-stimulated oxygen consumption and significantly decreased complex II SDHB subunit expression in placenta (-44.12 ± 5.88%; p < 0.001). Levels of mitochondrial content, Coenzyme Q and cellular ATP were conserved. Lipid peroxidation significantly decreased in IUGR-hearts (-39.02 ± 4.35%; p < 0.001), but not significantly increased in IUGR-placentas. Sirtuin3 protein expression significantly increased in IUGR-hearts (84.21 ± 31.58%; p < 0.05) despite conserved anti-oxidant SOD2 protein expression and activity in both tissues.
IUGR is associated with cardiac and placental mitochondrial CII dysfunction. Up-regulated expression of Sirtuin3 may explain attenuation of cardiac oxidative damage and preserved ATP levels under CII deficiency.
These findings may allow the design of dietary interventions to modulate Sirtuin3 expression and consequent regulation of mitochondrial imbalance associated with IUGR and derived cardiovascular remodeling.
Copyright © 2018 Elsevier B.V. All rights reserved.
• Keywords: Cardiovascular function, Fetal growth, Mitochondrial complex II, Mitochondrial dysfunction, Rabbit animal model, Sirtuin3 • Bioblast editor: Kandolf G • O2k-Network Lab: ES Barcelona Moren C
Labels: MiParea: Respiration, Developmental biology Pathology: Other
Organism: Rabbit Tissue;cell: Heart, Genital Preparation: Permeabilized tissue Enzyme: Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase
Pathway: N, ROX HRR: Oxygraph-2k