Gandhi Chintan, Uhal Bruce D
Department of Pediatrics/Neonatology, Michigan State University, USA.
Department of Physiology, Michigan State University, USA.
JSM Atheroscler. 2016;1(3). Epub 2016 Nov 2.
The renin-angiotensin system (RAS) has long been known as a regulator of blood pressure and fluid homeostasis. In past several decades, local renin-angiotensin systems have been discovered in various tissues and novel actions of angiotensin II (ANGII) have emerged as an immunomodulator and profibrotic molecule. The enzyme responsible for its synthesis, angiotensin-converting-enzyme (ACE), is present in high concentrations in lung tissue. ACE cleaves angiotensin I (ANG I) to generate angiotensin II (ANGII), whereas ACE2 inactivates ANGII and is a negative regulator of the system. The RAS has been implicated in the pathogenesis of pulmonary hypertension, acute lung injury and experimental lung fibrosis. Recent studies in animal and humans indicate that the RAS also plays a critical role in fetal and neonatal lung diseases. Further investigations are needed to better understand the role of RAS, ACE and ACE-2 in neonatal lung injury. With more clarity and understanding, the RAS and/or ACE-2 may ultimately prove to constitute potential therapeutic targets for the treatment of neonatal lung diseases. This manuscript reviews the evidence supporting a role for RAS in neonatal lung injury and discusses new possibilities for therapeutic approaches.
肾素-血管紧张素系统（RAS）长期以来一直被认为是血压和液体稳态的调节因子。在过去几十年中，已在各种组织中发现了局部肾素-血管紧张素系统，并且血管紧张素II（ANGII）作为一种免疫调节因子和促纤维化分子出现了新的作用。负责其合成的酶，即血管紧张素转换酶（ACE），在肺组织中高浓度存在。ACE将血管紧张素I（ANG I）裂解生成血管紧张素II（ANGII），而ACE2使ANGII失活，是该系统的负调节因子。RAS已被认为与肺动脉高压、急性肺损伤和实验性肺纤维化的发病机制有关。最近在动物和人类中的研究表明，RAS在胎儿和新生儿肺部疾病中也起关键作用。需要进一步研究以更好地了解RAS、ACE和ACE-2在新生儿肺损伤中的作用。随着认识更加清晰和深入，RAS和/或ACE-2最终可能被证明是治疗新生儿肺部疾病的潜在治疗靶点。本手稿综述了支持RAS在新生儿肺损伤中作用的证据，并讨论了治疗方法的新可能性。
