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Physiol Genomics. 2018 May 1;50(5):313-322. doi: 10.1152/physiolgenomics.00069.2017. Epub 2018 Feb 23.

DNA methylation signatures of pulmonary arterial smooth muscle cells in chronic thromboembolic pulmonary hypertension.

Wang Y1,2, Huang X2,3, Leng D1,2, Li J2,4, Wang L5, Liang Y1,2, Wang J6, Miao R1,2, Jiang T7,8.

Author information

1
Department of Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University , Beijing , People's Republic of China.
2
Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Institute of Respiratory Medicine , Beijing , People's Republic of China.
3
Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University , Beijing , People's Republic of China.
4
Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing , People's Republic of China.
5
Department of Pulmonary and Critical Care Medicine, Xuanwu Hospital, Capital Medical University , Beijing , People's Republic of China.
6
Department of Physiology, Capital Medical University , Beijing , People's Republic of China.
7
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University , Beijing , People's Republic of China.
8
Beijing Neurosurgical Institute, Capital Medical University , Beijing , People's Republic of China.

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease, which is often underpinned by vascular remodeling. Pulmonary arterial smooth muscle cells (PASMCs) are the main participants in vascular remodeling. However, their biological role in CTEPH is not entirely clear. In the present study, we analyzed the whole epigenome-wide DNA methylation profile of cultured PASMCs from CTEPH and control cell lines with the Illumina Human Methylation 450K BeadChip. A total of 6,829 significantly differentially methylated probes (DMPs) were detected between these two groups. Among these, 4,246 DMPs were hypermethylated, while 2,583 DMPs were hypomethylated. The functional enrichment analysis of 1,743 DMPs in the promoter regions and corresponding genes indicated that DNA hypermethylation and hypomethylation might be involved in the regulation of genes that have multifarious biological roles, including roles in cancer-related diseases, the regulation of the actin cytoskeleton, cell adhesion, and pattern specification processes. The observed methylations were categorized into the most important functions, including those involved in cell proliferation, immunity, and migration. We speculate that these methylations were most likely involved in the possible pathophysiology of CTEPH. Gene interaction analysis pertaining to signal networks confirmed that PIK3CA and PIK3R1 were important mediators in these whole networks. The mRNA levels of PIK3CA, HIC1, and SSH1 were verified by qPCR and corresponded with DNA methylation differences. Understanding epigenetic features associated with CTEPH may provide new insights into the mechanism that underlie this condition.

KEYWORDS:

DNA methylation profile; chronic thromboembolic pulmonary hypertension; functional enrichment analysis; pulmonary artery smooth muscle cells

[Indexed for MEDLINE]

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