Transient Neonatal High Oxygen Exposure Leads to Early Adult Cardiac Dysfunction, Remodeling, and Activation of the Renin-Angiotensin System
Transient Neonatal High Oxygen Exposure Leads to Early Adult Cardiac Dysfunction, Remodeling, and Activation of the Renin-Angiotensin System
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DOI：
10.1161/hypertensionaha.113.01760
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发表时间：
2014-01-01
期刊：
影响因子：
8.3
通讯作者：
Nuyt, Anne Monique
中科院分区：
文献类型：
--
作者：
Bertagnolli, Mariane;Huyard, Fanny;Nuyt, Anne Monique
围产期疾病（如早产）会影响成人的健康和疾病，特别是心血管系统。成年大鼠短暂的新生儿高 O-2 暴露（早产相关并发症的模型）会导致血压升高、血管僵化和肾素-血管紧张素系统激活功能障碍。我们假设新生儿高氧应激也会影响心肌结构、功能和肾素-血管紧张素系统成分的表达。 Sprague-Dawley 幼崽在出生后第 3 天至第 10 天与母亲一起饲养在 80% O-2 或室内空气（对照）中。对 4、7、12 周龄（超声心动图）和 16 周龄（心室内导管插入术）雄性 O-2 暴露大鼠与对照大鼠的左心室功能进行了评估。第 16 周时，暴露于 O-2 的大鼠心脏表现出心肌细胞肥大、纤维化增强、转化生长因子 1、衰老相关蛋白 p53 和 Rb 表达增加、血管紧张素 II 1 型 (AT1) 受体表达（蛋白和 AT1a/b mRNA）上调以及 AT2 受体下调。第 4 周（血压升高前），暴露于 O-2 的动物中心肌细胞表面积、纤维化、p53 和 AT1b 的表达显着增加，而 AT2 减少。连续输注血管紧张素 II 4 周（从 12 周开始）后，O-2 暴露的大鼠出现严重心力衰竭，与输注盐水的大鼠相比，心肌机械性能受损。新生大鼠短暂的 O-2 暴露会导致左心室肥厚、纤维化和功能障碍，并在压力超负荷下增加心力衰竭的易感性。这些结果与越来越多的早产儿群体有关，当面临与高血压、血管疾病和衰老相关的外周阻力增加时，他们可能面临更高的心功能障碍风险。
Perinatal conditions (such as preterm birth) can affect adult health and disease, particularly the cardiovascular system. Transient neonatal high O-2 exposure in rat in adulthood (a model of preterm birth-related complications) leads to elevated blood pressure, vascular rigidity, and dysfunction with renin-angiotensin system activation. We postulate that neonatal hyperoxic stress also affects myocardial structure, function, and expression of renin-angiotensin system components. Sprague-Dawley pups were kept with their mother in 80% O-2 or in room air (control) from days 3 to 10 of life. Left ventricular function was assessed in 4-, 7-, 12-week-old (echocardiography) and in 16-week-old (intraventricular catheterization) male O-2-exposed versus control rats. At 16 weeks, hearts from O-2-exposed rats showed cardiomyocyte hypertrophy, enhanced fibrosis, and increased expression of transforming growth factor-1, senescence-associated proteins p53 and Rb, upregulation of angiotensin II type 1 (AT1) receptor expression (protein and AT1a/b mRNA), and downregulation of AT2 receptors. At 4 weeks (before blood pressure increase), the expression of cardiomyocyte surface area, fibrosis, p53, and AT1b was significantly increased and AT2 decreased in O-2-exposed animals. After 4 weeks of continuous angiotensin II infusion (starting at 12 weeks), O-2-exposed rats developed severe heart failure, with impaired myocardial mechanical properties compared with saline-infused rats. Transient neonatal O-2 exposure in rats leads to left ventricular hypertrophy, fibrosis and dysfunction, and increased susceptibility to heart failure under pressure overload. These results are relevant to the growing population of individuals born preterm who may be at higher risk of cardiac dysfunction when faced with increased peripheral resistance associated with hypertension, vascular diseases, and aging.