TY - JOUR
T1 - Cardiac and placental mitochondrial characterization in a rabbit model of intrauterine growth restriction
AU - Guitart-Mampel, M.
AU - Gonzalez-Tendero, A.
AU - Niñerola, S.
AU - Morén, C.
AU - Catalán-Garcia, M.
AU - González-Casacuberta, I.
AU - Juárez-Flores, D. L.
AU - Ugarteburu, O.
AU - Matalonga, L.
AU - Cascajo, M. V.
AU - Tort, F.
AU - Cortés, A.
AU - Tobias, E.
AU - Milisenda, J. C.
AU - Grau, J. M.
AU - Crispi, F.
AU - Gratacós, E.
AU - Garrabou, G.
AU - Cardellach, F.
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
KW - Cardiovascular function
KW - Fetal growth
KW - Mitochondrial complex II
KW - Mitochondrial dysfunction
KW - Rabbit animal model
KW - Sirtuin3
UR - https://www.scopus.com/pages/publications/85042286936
U2 - 10.1016/j.bbagen.2018.02.006
DO - 10.1016/j.bbagen.2018.02.006
M3 - Article
C2 - 29452236
AN - SCOPUS:85042286936
SN - 0304-4165
VL - 1862
SP - 1157
EP - 1167
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 5
ER -
