title: Chronic pro-oxidative state and mitochondrial dysfunctions are more pronounced in fibroblasts from Down syndrome foeti with congenital heart defects.
abstract: Trisomy of chromosome 21 is associated to congenital heart defects in ∼50% of affected newborns. Transcriptome analysis of hearts from trisomic human foeti demonstrated that genes involved in mitochondrial function are globally downregulated with respect to controls, suggesting an impairment of mitochondrial function. We investigated here the properties of mitochondria in fibroblasts from trisomic foeti with and without cardiac defects. Together with the upregulation of Hsa21 genes and the downregulation of nuclear encoded mitochondrial genes, an abnormal mitochondrial cristae morphology was observed in trisomic samples. Furthermore, impairment of mitochondrial respiratory activity, specific inhibition of complex I, enhanced reactive oxygen species production and increased levels of intra-mitochondrial calcium were demonstrated. Seemingly, mitochondrial dysfunction was more severe in fibroblasts from cardiopathic trisomic foeti that presented a more pronounced pro-oxidative state. The data suggest that an altered bioenergetic background in trisomy 21 foeti might be among the factors responsible for a more severe phenotype. Since the mitochondrial functional alterations might be rescued following pharmacological treatments, these results are of interest in the light of potential therapeutic interventions.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71100, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Piccoli
authors.forename: Antonella
authors.initials: A
authors.lastname: Izzo
authors.forename: Rosella
authors.initials: R
authors.lastname: Scrima
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Bonfiglio
authors.forename: Rosanna
authors.initials: R
authors.lastname: Manco
authors.forename: Rosa
authors.initials: R
authors.lastname: Negri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarato
authors.forename: Olga
authors.initials: O
authors.lastname: Cela
authors.forename: Maria
authors.initials: M
authors.lastname: Ripoli
authors.forename: Marina
authors.initials: M
authors.lastname: Prisco
authors.forename: Flaviana
authors.initials: F
authors.lastname: Gentile
authors.forename: Gaetano
authors.initials: G
authors.lastname: Calì
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
authors.forename: Anna
authors.initials: A
authors.lastname: Conti
authors.forename: Lucio
authors.initials: L
authors.lastname: Nitsch
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Capitanio
mesh_terms: D037881:Aborted Fetus / Q000378:metabolism*; D004314:Down Syndrome / Q000150:complications / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006330:Heart Defects, Congenital / Q000150:complications / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D014314:Trisomy
chemical_list: D017382:Reactive Oxygen Species