In utero exposure to diesel exhaust is associated with alterations in neonatal cardiomyocyte transcription, DNA methylation and metabolic perturbation
| Autor: | Michael T. Chin, Jamie M. Goodson, Theo K. Bammler, Wei-Ming Chien, James W. MacDonald |
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| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | Particle and Fibre Toxicology, Vol 16, Iss 1, Pp 1-12 (2019) Particle and Fibre Toxicology |
| ISSN: | 1743-8977 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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