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Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR

Xue-Feng Xu1, Ying Lv2, Wei-Zhong Gu3, Li-Li Tang2, Jia-Kai Wei2, Li-Yan Zhang2 and Li-Zhong Du2*

Author Affiliations

1 Department of Respiratory Medicine, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P.R. China

2 Department of Neonatology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P.R. China

3 Department of Pathology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P.R. China

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Respiratory Research 2013, 14:20  doi:10.1186/1465-9921-14-20

Published: 14 February 2013

Abstract

Background

Accumulating evidence reveals that intrauterine growth retardation (IUGR) can cause varying degrees of pulmonary arterial hypertension (PAH) later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR.

Methods

The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC) were isolated from the rat lungs by magnetic-activated cell sorting (MACS). We investigated epigenetic regulation of the endothelin-1 (ET-1) gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia.

Results

The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α) binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling.

Conclusions

These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.

Keywords:
Epigenetics; Pulmonary arterial hypertension; Endothelial cells; Endothelin-1; Intrauterine growth retardation