Background:Approximately 10% of infants are born preterm. Preterm birth leads to short and long-term changes in cardiac shape and function. By using a rat model of neonatal high-oxygen (80%O₂) exposure, mimicking the premature hyperoxic transition to the extrauterine environment, we revealed a major role of the renin-angiotensin system peptide Angio II (angiotensin II) and its receptor AT1 (angiotensin receptor type 1) on neonatal O₂-induced cardiomyopathy. Here, we tested whether treatment with either orally active compounds of the peptides Angio-(1–7) or alamandine included in cyclodextrin could prevent postnatal cardiac remodeling and the programming of cardiomyopathy induced by neonatal high-O₂ exposure.Methods:Sprague-Dawley pups were exposed to room air or 80% O₂ from postnatal day 3 (P3) to P10. Neonatal rats were treated orally from P3 to P10 and assessed at P10 and P28. Left ventricular (LV) shapes were characterized by tridimensional computational atlases of ultrasound images in addition to histomorphometry.Results:At P10, high O₂-exposed rats presented a smaller, globular and hypertrophied LV shape versus controls. Treatment with cyclodextrin–Angio-(1–7) significantly improved LV function in the O₂-exposed neonatal rats and slightly changed LV shape. Cyclodextrin-alamandine and cyclodextrin–Angio-(1–7) treatments similarly reduced hypertrophy at P10 as well as LV remodeling and dysfunction at P28. Both treatments upregulated cardiac angiotensin-converting enzyme 2 in O₂-exposed rats at P10 and P28.Conclusions:Our findings demonstrate LV remodeling changes induced by O₂-stress and the potential benefits of treatments targeting the cardioprotective renin-angiotensin system axis, supporting the neonatal period as an important window for interventions aiming at preventing cardiomyopathy in people born preterm.

中文翻译：

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重塑早产心脏：将心脏肾素-血管紧张素系统转变为对暴露于新生儿高氧应激的大鼠的心脏保护

背景：大约 10% 的婴儿是早产儿。早产会导致心脏形状和功能的短期和长期变化。通过使用新生儿高氧（80%O ₂）暴露的大鼠模型，模拟过早的高氧过渡到宫外环境，我们揭示了肾素-血管紧张素系统肽 Angio II（血管紧张素 II）及其受体 AT1 的主要作用（血管紧张素受体 1 型）对新生儿 O ₂诱导的心肌病的影响。在这里，我们测试了使用包含在环糊精中的肽 Angio-(1-7) 或阿勒曼定的口服活性化合物治疗是否可以预防出生后心脏重塑和新生儿高 O _{2诱导的心肌病的程序化。}暴露。方法：从出生后第 3 天 (P3) 到 P10，将 Sprague-Dawley 幼崽暴露在室内空气或 80% O _2中。从 P3 到 P10 对新生大鼠进行口服治疗，并在 P10 和 P28 进行评估。除了组织形态计量学之外，左心室 (LV) 形状的特征还包括超声图像的三维计算图谱。结果：在 P10 时，与对照组相比，高 O ₂暴露的大鼠呈现出更小、球状和肥大的 LV 形状。环糊精-Angio-(1-7) 治疗显着改善了 O _{2中的 LV 功能}-暴露的新生大鼠和轻微改变的 LV 形状。环糊精-阿拉曼定和环糊精-Angio-(1-7) 治疗同样减少了 P10 的肥大以及 P28 的 LV 重塑和功能障碍。两种治疗在 P10 和 P28上调 O ₂暴露大鼠的心脏血管紧张素转化酶 2。结论：我们的研究结果表明 O ₂应激诱导的 LV 重塑变化以及针对心脏保护性肾素-血管紧张素系统轴的治疗的潜在益处，支持新生儿期是旨在预防早产儿心肌病的干预措施的重要窗口。