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In utero exposure to diesel exhaust is associated with alterations in neonatal cardiomyocyte transcription, DNA methylation and metabolic perturbation
- Source :
- Particle and Fibre Toxicology, Vol 16, Iss 1, Pp 1-12 (2019), Particle and Fibre Toxicology
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Background Developmental exposure to particulate matter air pollution is harmful to cardiovascular health, but the mechanisms by which this exposure mediates susceptibility to heart disease is poorly understood. We have previously shown, in a mouse model, that gestational exposure to diesel exhaust (DE) results in increased cardiac hypertrophy, fibrosis and susceptibility to heart failure in the adult offspring following transverse aortic constriction. Results In this study, we have analyzed gene expression in neonatal cardiomyocytes after gestational exposure by RNA-sequencing and have identified 300 genes that are dysregulated, including many involved in cardiac metabolism. We subsequently determined that these cardiomyocytes exhibit reduced metabolic activity as measured by Seahorse extracellular flux analysis. We also surveyed for modifications in DNA methylation at global regulatory regions using reduced representation bisulfite sequencing and found hypomethylation of DNA in neonatal cardiomyocytes isolated from in utero DE exposed neonates. Conclusion We have demonstrated that in utero exposure to diesel exhaust alters the neonatal cardiomyocyte transcriptional and epigenetic landscapes, as well as the metabolic capability of these cells. Understanding how exposure alters the developing heart through dysregulation of gene expression, metabolism and DNA methylation is vital for identifying therapeutic interventions for air pollution-related heart failure.
- Subjects :
- Heart disease
Health, Toxicology and Mutagenesis
lcsh:Industrial hygiene. Industrial welfare
PM2.5
Biology
Toxicology
Andrology
03 medical and health sciences
Pregnancy
lcsh:RA1190-1270
Gene expression
medicine
Animals
Myocytes, Cardiac
Epigenetics
Diesel
Vehicle Emissions
lcsh:Toxicology. Poisons
Inhalation Exposure
0303 health sciences
DNA methylation
Research
030311 toxicology
General Medicine
Methylation
medicine.disease
3. Good health
Mice, Inbred C57BL
Metabolism
Animals, Newborn
Maternal Exposure
13. Climate action
In utero
Prenatal Exposure Delayed Effects
Heart failure
Reduced representation bisulfite sequencing
Metabolome
Female
Particulate Matter
Transcriptome
Transcription
lcsh:HD7260-7780.8
Subjects
Details
- ISSN :
- 17438977
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Particle and Fibre Toxicology
- Accession number :
- edsair.doi.dedup.....0b033aaf13da8725fca207b628bd35dd