DNA methylation profiling reveals novel pathway implicated in cardiovascular diseases of diabetes

Shengqing Hu; Lulu Chen; Tianshu Zeng; Wenyi Wang; Yan Yan; Kangli Qiu; Yajuan Xie; Yunfei Liao

doi:10.3389/fendo.2023.1108126

DNA methylation profiling reveals novel pathway implicated in cardiovascular diseases of diabetes

Front Endocrinol (Lausanne). 2023 Feb 15:14:1108126. doi: 10.3389/fendo.2023.1108126. eCollection 2023.

Authors

Shengqing Hu^{1

2}, Lulu Chen^{1

2}, Tianshu Zeng^{1

2}, Wenyi Wang^{1

2}, Yan Yan^{1

2}, Kangli Qiu^{1

2}, Yajuan Xie^{1

2}, Yunfei Liao^{1

2}

Affiliations

¹ Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China.

Abstract

Objective: Epigenetics was reported to mediate the effects of environmental risk factors on disease pathogenesis. We intend to unleash the role of DNA methylation modification in the pathological process of cardiovascular diseases in diabetes.

Methods: We screened differentially methylated genes by methylated DNA immunoprecipitation chip (MeDIP-chip) among the enrolled participants. In addition, methylation-specific PCR (MSP) and gene expression validation in peripheral blood of participants were utilized to validate the DNA microarray findings.

Results: Several aberrantly methylated genes have been explored, including phospholipase C beta 1 (PLCB1), cam kinase I delta (CAMK1D), and dopamine receptor D5 (DRD5), which participated in the calcium signaling pathway. Meanwhile, vascular endothelial growth factor B (VEGFB), placental growth factor (PLGF), fatty acid transport protein 3 (FATP3), coagulation factor II, thrombin receptor (F2R), and fatty acid transport protein 4 (FATP4) which participated in vascular endothelial growth factor receptor (VEGFR) signaling pathway were also found. After MSP and gene expression validation in peripheral blood of participants, PLCB1, PLGF, FATP4, and VEGFB were corroborated.

Conclusion: This study revealed that the hypomethylation of VEGFB, PLGF, PLCB1, and FATP4 might be the potential biomarkers. Besides, VEGFR signaling pathway regulated by DNA methylation might play a role in the cardiovascular diseases' pathogenesis of diabetes.

Keywords: DNA methylation; cardiovascular diseases; diabetes; methylated DNA immunoprecipitation; signaling pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cardiovascular Diseases*
DNA Methylation
Diabetes Mellitus*
Fatty Acid Transport Proteins
Humans
Placenta Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor B

Substances

Fatty Acid Transport Proteins
Placenta Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor B

Grants and funding

This work was supported by National Natural Science Foundation of China Grants (grant numbers 81070648, 81471069, 81100580, and 82070830), Science and Technology Research Project of Hubei Province Public Welfare (2013BCB016) and Key R&D plan of Hubei Province (2022BCA036).