AEPC-YIA session（III-AEPCYIA）

[III-AEPCYIA-01] Perinatal Hypoxia Aggravates Occlusive Pulmonary Vasculopathy In Rats Later In Life: Association With Epigenetic Changes

^○Hironori Oshita^1,2, Yoshihide Mitani², Hirofumi Sawada^1,3, Naoki Tsuboya¹, Junko Maruyama⁴, Noriko Yodoya¹, Hiroyuki Ohashi¹, Kazunobu Oya¹, Shinji Saitoh², Kazuo Maruyama³, Masahiro Hirayama¹ (1.Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan, 2.Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan, 3.Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan, 4.Department of Clinical Engineering, Suzuka University of Medical Science, Mie, Japan)

Keywords:pulmonary hypertension, perinatal hypoxia, DNA methylation

【Background】 To test the hypothesis that perinatal hypoxia (PeriHx) aggravates pulmonary arterial hypertension (PAH) and occlusive pulmonary vascular diseases (PVD) in SUGEN/Hypoxia (SuHx)-induced PAH rats, and to investigate the mechanism of this exacerbation.【Methods】 PVD was induced in rats with/without perinatal hypoxia (from embryonic day 14 to postnatal day 3) by injecting SU5416 at 7 weeks of age and subsequent exposure to hypoxia for 3 weeks. Hemodynamic and morphological analyses were performed in rats with/without perinatal hypoxia at 7 weeks of age (baseline rats, n=12) and at 15 weeks of age in 4 groups of rats: SU5416/hypoxia or control rats with/without perinatal hypoxia (8 weeks after SU5416 injection, n=40). Pulmonary artery smooth muscle cells (PASMCs) from the baseline rats with/without perinatal hypoxia were used to assess cell proliferation, inflammation and genomic DNA methylation profile.【Results】 Although perinatal hypoxia did not affect survival, physiological or pathological parameters at baseline or at the end of the experimental period in controls, perinatal hypoxia decreased weight gain and survival rate, and increased right ventricular systolic pressure, right ventricular hypertrophy, and indices of PVD in SU5416/hypoxia rats. Perinatal hypoxia accelerated the proliferation and inflammation of cultured PASMCs from baseline rats, which was associated with DNA methylation.【Conclusion】 PeriHx worsened survival, hemodynamics, and PVD in PAH rats, and PeriHx was a risk factor for PAH, suggesting an epigenesis-mediated mechanism for PAH.