Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/123505
Title: Cardiac and placental mitochondrial characterization in a rabbit model of intrauterine growth restriction
Author: Guitart Mampel, Mariona
Gonzalez-Tendero, Anna
Niñerola, S.
Morén Núñez, Constanza
Catalán García, Marc
González-Casacuberta, I.
Juárez-Flores, D. L.
Ugarteburu, O.
Matalonga, L.
Cascajo, M. V.
Tort, F.
Cortés, A.
Tobias, E.
Milisenda, José
Grau Junyent, Josep M. (Josep Maria)
Crispi Brillas, Fàtima
Gratacós Solsona, Eduard
Garrabou Tornos, Glòria
Cardellach, Francesc
Keywords: Cor
Creixement fetal
Conills
Obstetrícia
Mitocondris
Heart
Fetal growth
Rabbits
Obstetrics
Mitochondria
Issue Date: 13-Feb-2018
Publisher: Elsevier B.V.
Abstract: BACKGROUND: 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. METHODS: Hearts and placentas from 16 IUGR-offspring and 14 controls were included to characterize mitochondrial function. RESULTS: 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. CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.
Note: Versió postprint del document publicat a: https://doi.org/10.1016/j.bbagen.2018.02.006
It is part of: Biochimica et Biophysica Acta-General Subjects, 2018, vol. 1862, num. 5, p. 1157-1167
URI: http://hdl.handle.net/2445/123505
Related resource: https://doi.org/10.1016/j.bbagen.2018.02.006
ISSN: 0304-4165
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Files in This Item:
File Description SizeFormat 
677211.pdf2.02 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons