The importance of sphingolipids and reactive oxygen species in cardiovascular development

Poloni, Joice de Faria; Chapola, Henrique; Feltes, Bruno César; Bonatto, Diego

doi:10.1111/boc.201400008

Cited by 20 publications

(16 citation statements)

References 97 publications

(203 reference statements)

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“…Plasmalogens may have a protective role in P1 mice hearts since they have been shown to protect against ROS-induced lipid peroxidation. Furthermore, low levels of plasmalogens are associated with increased cardiovascular mortality (Zoeller et al, 1988 ; Stenvinkel et al, 2004 ), and sphingolipid metabolism is upregulated in P7 hearts under oxidative stress (Nikolova-Karakashian and Reid, 2011 ; de Faria Poloni et al, 2014 ). An upsurge in ceramide levels can activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which in turn aggregates to lipid rafts and together with Src and Rac1 forms functional redox signaling platforms.…”

Section: Discussionmentioning

confidence: 99%

Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach

et al. 2018

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The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury that is lost within the first week of its life. In order to elucidate the molecular mechanisms taking place in the mouse heart during this critical period we applied an untargeted combinatory multiomics approach using large-scale mass spectrometry-based quantitative proteomics, metabolomics and mRNA sequencing on hearts from 1-day-old and 7-day-old mice. As a result, we quantified 1.937 proteins (366 differentially expressed), 612 metabolites (263 differentially regulated) and revealed 2.586 differentially expressed gene loci (2.175 annotated genes). The analyses pinpointed the fructose-induced glycolysis-pathway to be markedly active in 1-day-old neonatal mice. Integrated analysis of the data convincingly demonstrated cardiac metabolic reprogramming from glycolysis to oxidative phosphorylation in 7-days old mice, with increases of key enzymes and metabolites in fatty acid transport (acylcarnitines) and β-oxidation. An upsurge in the formation of reactive oxygen species and an increase in oxidative stress markers, e.g., lipid peroxidation, altered sphingolipid and plasmalogen metabolism were also evident in 7-days mice. In vitro maintenance of physiological fetal hypoxic conditions retained the proliferative capacity of cardiomyocytes isolated from newborn mice hearts. In summary, we provide here a holistic, multiomics view toward early postnatal changes associated with loss of a tissue regenerative capacity in the neonatal mouse heart. These results may provide insight into mechanisms of human cardiac diseases associated with tissue regenerative incapacity at the molecular level, and offer a prospect to discovery of novel therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach

et al. 2018

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“…Ceramide and sphingosine can inhibit proliferation and induce apoptosis and inflammation, while the metabolite S1P has been implicated in protection from apoptosis and in anti‐inflammatory activity (Gomez‐Munoz et al, ). These close connections between the sphingolipid metabolites and angiogenesis (de Faria Poloni, Chapola, Feltes, & Bonatto, ) or inflammation may provide a novel explanation for MA. S1P signaling is thought to be essential in vascular formation within the uteroplacental unit and in fetomaternal immunological interactions, and derangements in these processes could result in pregnancy complications, including implantation failure, preeclampsia and preterm labor (Nagamatsu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolomic profile and potential biomarkers for missed abortion

Hou

et al. 2016

Biomedical Chromatography

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A missed abortion (MA) is an in utero death of the embryo or fetus before the 20th week of gestation with retained products of conception, and this condition is currently common in China. In order to discover novel biomarkers for MA, ultrahigh performance liquid chromatography was applied to study plasma metabolite profiles for 33 patients with MA and 29 control subjects. Thirty-seven differential plasma metabolites were found to discriminate between the two groups in the initial cohort (15 subjects with MA and 15 healthy controls). The feasibility of using these potential biomarkers to predict MA was further evaluated in the validation cohort (18 subjects with MA and 14 healthy controls) and 15 had an area under the receiver operating characteristic curve of >0.80, making them satisfactory. Tryptophan metabolism and sphingolipid metabolism were identified as important potential target pathways for MA using metabolic pathway impact analysis. Furthermore, three of the 15 satisfactory metabolites (glyceric acid, indole and sphingosine) were combined to establish a predictive model with 100% sensitivity and 100% specificity in the validation cohort. Taken together, these results suggest that MA results in significant disturbance of metabolism and those various novel biomarkers have satisfactory diagnostic and predictive power for MA.

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“…In the cardiovascular system, ROS is considered as "double-edged sword," for example, ROS could participate in the cell survival signaling during ischemic events (Kalogeris et al, 2014). In terms of heart development, ROS is a modulator to sphingolipids, an important factor in heart development (de Faria Poloni et al, 2014). However, cardiomyocytes are known to be vulnerable to excessive ROS generation, which is a molecular mechanism of cardiotoxicants such as doxorubicin (Ludke et al, 2012).…”

Section: Mg/mlmentioning

confidence: 99%

Perfluorooctanoic acid‐induced toxicity in primary cultures of chicken embryo cardiomyocytes

Jiang

et al. 2015

Environmental Toxicology

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Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that induces developmental cardiotoxicity. It is detectable in late stage chicken embryos and hatchling chickens. To investigate mechanism(s) of cardiotoxicity, primary cultures of cardiomyocytes were prepared from 10-day-old chicken embryos that were (A) pre-exposed to vehicle or 2 mg of PFOA/kg of egg weight in ovo or (B) incubated with PFOA in vitro at concentrations ranging from 0 to 100 µg/mL in medium for 1 or 36 h. When viability was assessed, survival of cardiomyocytes prepared from pre-exposed embryos did not differ from vehicle controls, even under conditions of serum starvation designed to challenge the cells. However, 1 h of exposure to 100 µg/mL of PFOA in vitro and 36 h of exposure to 75 and 100 µg/mL PFOA in vitro decreased viability. When contractility was evaluated, cardiomyocytes cultured from pre-exposed embryos exhibited decreases in time to maximum departure velocity and cell length at peak contraction, whereas cardiomyocytes exposed in vitro exhibited a reduction in the 50% relaxation time at a concentration of 1 µg/mL relative to vehicle controls. Morphological assessment revealed decreased cardiomyocytes axial length following in ovo PFOA exposure and 24 h in vitro PFOA 50 µg/mL exposure. Reactive oxygen species (ROS) generation, which was evaluated only in cardiomyocytes exposed to PFOA in vitro, was significantly elevated following incubation with 50 µg/mL of PFOA for 1 h. These data indicate that while in vitro exposure to relatively high concentrations of PFOA can induce cytotoxicity and ROS, developmental cardiotoxicity observed in ovo is not likely mediated via PFOA-induced overt cytotoxicity, but likely by altering early cardiac morphologic and function processes. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1580-1590, 2016.

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The importance of sphingolipids and reactive oxygen species in cardiovascular development

Cited by 20 publications

References 97 publications

Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach

Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach

Plasma metabolomic profile and potential biomarkers for missed abortion

Perfluorooctanoic acid‐induced toxicity in primary cultures of chicken embryo cardiomyocytes

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