“Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.”
Chronic kidney disease (CKD) related cardiovascular disease (CVD) is characterized by vascular remodelling with well-established structural and functional changes in the vascular wall such as arterial stiffness, matrix deposition, and calcification. These phenotypic changes resemble pathology seen i...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-07-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2020.1819666 |
| _version_ | 1797678858213785600 |
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| author | Athina Dritsoula Maria Kislikova Amin Oomatia Amy P. Webster Stephan Beck Markella Ponticos Ben Lindsey Jill Norman David C. Wheeler Thomas Oates Ben Caplin |
| author_facet | Athina Dritsoula Maria Kislikova Amin Oomatia Amy P. Webster Stephan Beck Markella Ponticos Ben Lindsey Jill Norman David C. Wheeler Thomas Oates Ben Caplin |
| author_sort | Athina Dritsoula |
| collection | DOAJ |
| description | Chronic kidney disease (CKD) related cardiovascular disease (CVD) is characterized by vascular remodelling with well-established structural and functional changes in the vascular wall such as arterial stiffness, matrix deposition, and calcification. These phenotypic changes resemble pathology seen in ageing, and are likely to be mediated by sustained alterations in gene expression, which may be caused by epigenetic changes such as tissue-specific DNA methylation. We aimed to investigate tissue specific changes in DNA methylation that occur in CKD-related CVD. Genome-wide DNA methylation changes were examined in bisulphite converted genomic DNA isolated from the vascular media of CKD and healthy arteries. Methylation-specific PCR was used to validate the array data, and the association between DNA methylation and gene and protein expression was examined. The DNA methylation age was compared to the chronological age in both cases and controls. Three hundred and nineteen differentially methylated regions (DMR) were identified spread across the genome. Pathway analysis revealed that DMRs associated with genes were involved in embryonic and vascular development, and signalling pathways such as TGFβ and FGF. Expression of top differentially methylated gene HOXA5 showed a significant negative correlation with DNA methylation. Interestingly, DNA methylation age and chronological age were highly correlated, but there was no evidence of accelerated age-related DNA methylation in the arteries of CKD patients. In conclusion, we demonstrated that differential DNA methylation in the arterial tissue of CKD patients represents a potential mediator of arterial pathology and may be used to uncover novel pathways in the genesis of CKD-associated complications. |
| first_indexed | 2024-03-11T23:06:02Z |
| format | Article |
| id | doaj.art-f0625af892b84ce089e63ce98d6f558f |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:06:02Z |
| publishDate | 2021-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-f0625af892b84ce089e63ce98d6f558f2023-09-21T13:09:24ZengTaylor & Francis GroupEpigenetics1559-22941559-23082021-07-0116771872810.1080/15592294.2020.18196661819666“Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.”Athina Dritsoula0Maria Kislikova1Amin Oomatia2Amy P. Webster3Stephan Beck4Markella Ponticos5Ben Lindsey6Jill Norman7David C. Wheeler8Thomas Oates9Ben Caplin10UCLUCLUCLCancer Institute, UCLCancer Institute, UCLUCLUCLUCLUCLUCLUCLChronic kidney disease (CKD) related cardiovascular disease (CVD) is characterized by vascular remodelling with well-established structural and functional changes in the vascular wall such as arterial stiffness, matrix deposition, and calcification. These phenotypic changes resemble pathology seen in ageing, and are likely to be mediated by sustained alterations in gene expression, which may be caused by epigenetic changes such as tissue-specific DNA methylation. We aimed to investigate tissue specific changes in DNA methylation that occur in CKD-related CVD. Genome-wide DNA methylation changes were examined in bisulphite converted genomic DNA isolated from the vascular media of CKD and healthy arteries. Methylation-specific PCR was used to validate the array data, and the association between DNA methylation and gene and protein expression was examined. The DNA methylation age was compared to the chronological age in both cases and controls. Three hundred and nineteen differentially methylated regions (DMR) were identified spread across the genome. Pathway analysis revealed that DMRs associated with genes were involved in embryonic and vascular development, and signalling pathways such as TGFβ and FGF. Expression of top differentially methylated gene HOXA5 showed a significant negative correlation with DNA methylation. Interestingly, DNA methylation age and chronological age were highly correlated, but there was no evidence of accelerated age-related DNA methylation in the arteries of CKD patients. In conclusion, we demonstrated that differential DNA methylation in the arterial tissue of CKD patients represents a potential mediator of arterial pathology and may be used to uncover novel pathways in the genesis of CKD-associated complications.http://dx.doi.org/10.1080/15592294.2020.1819666chronic kidney disease (ckd)cardiovascular disease (cvd)vascular remodellingarterial ageingdna methylationepigenetics |
| spellingShingle | Athina Dritsoula Maria Kislikova Amin Oomatia Amy P. Webster Stephan Beck Markella Ponticos Ben Lindsey Jill Norman David C. Wheeler Thomas Oates Ben Caplin “Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.” Epigenetics chronic kidney disease (ckd) cardiovascular disease (cvd) vascular remodelling arterial ageing dna methylation epigenetics |
| title | “Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.” |
| title_full | “Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.” |
| title_fullStr | “Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.” |
| title_full_unstemmed | “Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.” |
| title_short | “Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.” |
| title_sort | epigenome wide methylation profile of chronic kidney disease derived arterial dna uncovers novel pathways in disease associated cardiovascular pathology |
| topic | chronic kidney disease (ckd) cardiovascular disease (cvd) vascular remodelling arterial ageing dna methylation epigenetics |
| url | http://dx.doi.org/10.1080/15592294.2020.1819666 |
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