Figure 2.

Epigenetic regulatory mechanisms of developmental origin of PAH: IUGR rats become hypersensitive to hypoxia as a result of PH along with an increased expression of ET-1, which is involved in contraction of pulmonary vascular. The acetylation of histone H3, H3K9/18, and H4 of ET-1 gene in IUGR-hypoxia rats PAEC accompanied with enriched transcription factor HIF-1α was found. The increased ET-1 activates ET receptors in PASMC that results in vasoconstriction and proliferation. In the EUGR induced PAH rat model, the levels of H3K27me3 of the eNOS gene were significantly higher. EUGR also caused H3K27me3 and methylation of a CpG site of Notch1 gene. This decreases the expression of eNOS mRNA, Notch1 mRNA and its downstream gene HES1 as a consequence, which impairs anti-proliferation and vasodilation.