DNA Methylation-Reprogrammed Ang II (Angiotensin II) Type 1 Receptor-Early Growth Response Gene 1-Protein Kinase C ? Axis Underlies Vascular Hypercontractility in Antenatal Hypoxic Offspring

As the most common clinical stress during mid and late pregnancy, antenatal hypoxia has profound adverse effects on individual’s vascular health later in life, but underlying mechanisms are still not understood. The purpose of this study was to reveal acquired dysfunction offspring imposed by hypoxia. Pregnant rats were housed a normoxic or hypoxic (10.5% oxygen) chamber from gestation day 10 21. Male euthanized at gestational 21 (fetus) postnatal 16 weeks old (adult offspring). Mesenteric arteries collected for examining Ang II (angiotensin II)–mediated contractility, gene expression, promoter methylation. Antenatal increased sensitivity II, which resulted an upregulated AT1R type 1 receptor). correlated with hypomethylation-mediated activated transcription Agtr1a (alpha subtype AT1R). In addition, we presented evidences that there AT1R-Egr1 (early growth response 1)-PKC? (? isoform protein kinase C) axis vasculature; could modulate PKC? expression via upregulating Egr1; Egr1 mediated activation binding sites promoter. Overall, AT1R-Egr1-PKC? vasculature, eventually predisposed hypercontractility. This is first description outcomes offspring, strongly associated reprogrammed DNA methylation-mediated epigenetic mechanism, advancing understanding toward influence factors early life long-term health.