Methylome of Skeletal Muscle Tissue in Patients with Hypertension and Diabetes Undergoing Cardiopulmonary Bypass

Abstract

Background: Epigenomic changes occurring during surgery have been neglected in research; diabetes and hypertension can affect the epigenome but little is known about the epigenetics of skeletal muscle (SKM). Methods: DNA methylation was profiled via Illumina MethylationEPIC arrays in SKM samples obtained at the beginning and end of heart surgery with cardiopulmonary bypass. Results: Methylation in patients with hypertension and diabetes was significantly different, more so for uncontrolled diabetes; hypertension alone produced minimal effect. The affected pathways involved IL-1, IL-12, IL-18, TNF-α, IFN-γ, VEGF, NF-κB and Wnt signaling, apoptosis and DNA damage response. Significant changes occurred during surgery and included loci in the Hippo–YAP/TAZ pathway. Conclusion: Cardiopulmonary bypass surgery affects the SKM methylome, and the combination of hypertension and diabetes induces changes in the SKM epigenome in contrast to hypertension alone.

Keywords::

• cardiac surgery
• cardiopulmonary bypass (CPB)
• diabetes
• DNA methylation
• epigenomics
• hypertension
• skeletal muscle

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0388

Author contributions

G Aghagoli, A Del Re, Z Zhang, AA Gheit, R Phillips and F Sellke participated in surgery, recruited patients and collected patient samples. G Aghagoli and A Del Re identified patient samples and analyzed patient information. G Aghagoli co-ordinated the study and was in charge of sample storage and transportation. N Yano processed samples and isolated DNA, performed quality control and validation. F Sellke and A Fedulov conceived and supervised the study. F Sellke led the surgical team and performed surgeries and postoperative care. A Fedulov processed DNA samples and analyzed data. G Aghagoli, A Del Re, N Yano, F Sellke and A Fedulov coauthored the manuscript. All authors participated in drafting and/or revising the paper, provided important intellectual contributions and approved the manuscript.

Financial & competing interests disclosure

This study is supported in part by NIEHS grant R01 ES030227 and by Rhode Island Hospital Department of Surgery funds (A Fedulov). The study was also supported by the National Heart, Lung, and Blood Institute HL-46716 (F Sellke) and HL128831 (F Sellke). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval form Rhode Island Hospital Institutional Review Board (IRB no. 225612-53) for all human experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

The data informing this manuscript are publicly available through NCBI GEO database (GSE173613).

Additional information

Funding

This study is supported in part by NIEHS grant R01 ES030227 and by Rhode Island Hospital Department of Surgery funds (A Fedulov). The study was also supported by the National Heart, Lung, and Blood Institute HL-46716 (F Sellke) and HL128831 (F Sellke). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.