Abstract

Despite the progressive improvements in diagnosis and therapy during the first 20 years of this century, the morbidity and mortality of patients with heart failure (HF) remain high, resulting in an enormous health and economic burden. Only a further improvement in understanding the pathophysiological mechanisms related to the development of cardiac injury and dysfunction can allow more innovative and personalized approaches to HF management. The renin–angiotensin system (RAS) has a critical role in cardiovascular physiology by regulating blood pressure and electrolyte balance. The RAS is mainly regulated by both angiotensin converting enzyme (ACE) and type 2 angiotensin converting enzyme (ACE2). However, the balance between the various peptides and peptidases constituting the RAS/ACE pathway remains in great part unraveled in patients with HF. This review summarizes the role of the RAS/ACE axis in cardiac physiology and HF pathophysiology as well as some analytical issues relevant to the clinical and laboratory assessment of inter-relationships between these two systems. There is evidence that RAS peptides represent a dynamic network of peptides, which are altered in different HF states and influenced by medical therapy. However, the mechanisms of signal transduction have not been fully elucidated under physiological and pathophysiological conditions. Further investigations are necessary to explore novel molecular mechanisms related to the RAS, which will provide alternative therapeutic agents. Moreover, monitoring the circulating levels of active RAS peptides in HF patients may enable a personalized approach by facilitating assessment of the pathophysiological status of several cardiovascular diseases and thus better selection of therapies for HF patients.

摘要

尽管在本世纪的前 20 年诊断和治疗取得了进步，但心力衰竭 (HF) 患者的发病率和死亡率仍然很高，导致了巨大的健康和经济负担。只有进一步了解与心脏损伤和功能障碍发展相关的病理生理机制，才能为心衰管理提供更具创新性和个性化的方法。肾素-血管紧张素系统 (RAS) 通过调节血压和电解质平衡在心血管生理学中发挥关键作用。RAS 主要受血管紧张素转化酶 (ACE) 和 2 型血管紧张素转化酶 (ACE2) 的调控。然而，构成 RAS/ACE 途径的各种肽和肽酶之间的平衡在 HF 患者中仍有很大一部分未解决。本综述总结了 RAS/ACE 轴在心脏生理学和 HF 病理生理学中的作用，以及与这两个系统之间相互关系的临床和实验室评估相关的一些分析问题。有证据表明 RAS 肽代表一个动态的肽网络，在不同的 HF 状态下会发生改变并受药物治疗的影响。然而，在生理和病理生理条件下，信号转导的机制尚未完全阐明。需要进一步研究以探索与 RAS 相关的新分子机制，这将提供替代治疗剂。而且，