Department of Neonatology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P,R, China.
Respir Res. 2013 Feb 14;14(1):20. doi: 10.1186/1465-9921-14-20.
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.
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.
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.
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.
越来越多的证据表明，宫内生长迟缓（IUGR）会导致生命后期出现不同程度的肺动脉高压（PAH）。此外，表观遗传学在胎儿起源的成人疾病中起着重要作用。本研究旨在探讨表观遗传学在 IUGR 后 PAH 发展中的作用。
通过孕期母体营养不良建立 IUGR 大鼠模型。通过磁激活细胞分选（MACS）从大鼠肺中分离肺血管内皮细胞（PVEC）。我们研究了 IUGR 大鼠 1 天和 6 周时 PVEC 中内皮素-1（ET-1）基因的表观遗传调控，以及 IUGR 大鼠对缺氧的反应。
母体营养限制增加了 IUGR 新生大鼠 PVEC 中 ET-1 基因启动子的组蛋白乙酰化和缺氧诱导因子-1α（HIF-1α）结合水平，并持续至出生后 6 周。这些表观遗传变化可能导致 IUGR 大鼠在生命后期对缺氧高度敏感，从而导致更严重的 PAH 或肺血管重塑。
这些发现表明，表观遗传学与 IUGR 后缺氧性 PAH 的发展密切相关，为改善 IUGR 相关 PAH 的预防和治疗提供了新的思路。
