Guang Yang, Abbas Khan, Wei Liang, Zibo Xiong, Johannes Stegbauer
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引用次数: 0
摘要
主动脉瘤(AA)是一种死亡率很高的主动脉疾病,除手术治疗外,目前还没有其他有效的预防或治疗方法。肾素-血管紧张素系统(RAS)是调节血管健康的重要内分泌系统。ACE2/Ang-(1-7)/MasR 轴可以拮抗 ACE/Ang II/AT1R 轴激活对血管功能障碍、动脉粥样硬化和动脉瘤发展的不利影响,从而为预防和治疗 AA 提供了一个重要的治疗靶点。然而,针对 Ang-(1-7)/MasR 通路的产品仍缺乏临床验证。本综述将概述 AA 的流行病学,包括胸腔、腹腔和胸腹腔 AA,以及当前的诊断和治疗策略。由于腹腔 AA(AAA)的发病率最高,研究也最广泛,我们将重点讨论 AAA,以解释 RAS 在其发病中的作用、Ang-(1-7)/MasR 的保护功能以及相关机制。我们还将描述激动剂和拮抗剂的作用,提出工程和给药方面的改进建议,并为 Ang-(1-7)/MasR 的临床潜力提供证据,讨论临床应用的风险和解决方案。这项研究将加深我们对 AA 的了解,并为治疗干预提供新的可能性和有前景的目标。
Aortic aneurysm: pathophysiology and therapeutic options
Aortic aneurysm (AA) is an aortic disease with a high mortality rate, and other than surgery no effective preventive or therapeutic treatment have been developed. The renin–angiotensin system (RAS) is an important endocrine system that regulates vascular health. The ACE2/Ang-(1–7)/MasR axis can antagonize the adverse effects of the activation of the ACE/Ang II/AT1R axis on vascular dysfunction, atherosclerosis, and the development of aneurysms, thus providing an important therapeutic target for the prevention and treatment of AA. However, products targeting the Ang-(1–7)/MasR pathway still lack clinical validation. This review will outline the epidemiology of AA, including thoracic, abdominal, and thoracoabdominal AA, as well as current diagnostic and treatment strategies. Due to the highest incidence and most extensive research on abdominal AA (AAA), we will focus on AAA to explain the role of the RAS in its development, the protective function of Ang-(1–7)/MasR, and the mechanisms involved. We will also describe the roles of agonists and antagonists, suggest improvements in engineering and drug delivery, and provide evidence for Ang-(1–7)/MasR's clinical potential, discussing risks and solutions for clinical use. This study will enhance our understanding of AA and offer new possibilities and promising targets for therapeutic intervention.