Classical and Counter-Regulatory Renin-Angiotensin System: Potential Key Roles in COVID-19 Pathophysiology.
Classical and Counter-Regulatory Renin-Angiotensin System: Potential Key Roles in COVID-19 Pathophysiology.
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DOI：
10.1016/j.cjco.2021.04.004
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Barhoumi T
中科院分区：
文献类型：
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作者：
Almutlaq M;Alamro AA;Alroqi F;Barhoumi T
在当前的COVID-19大流行中，严重急性呼吸综合征冠状病毒2型使用血管紧张素转换酶-2（ACE-2）受体进入细胞，导致ACE-2功能障碍和下调，从而扰乱了经典和反调节的肾素-血管紧张素系统（RAS）之间的平衡，有利于经典RAS。RAS失调是多种心血管疾病的主要特征之一，因此，调节该系统是主要的治疗目标。RAS拮抗剂-特别是血管紧张素转换酶抑制剂（ACEIs）和血管紧张素II 1型受体阻滞剂（ARB）-通常用于治疗高血压和心血管疾病。心血管疾病患者是COVID-19合并症患者中最常见的人群。在这场大流行开始时，ACEI和ARB的使用出现了困境，可能会加重COVID-19患者的心血管和肺功能障碍。来自不同国家和医院的紧急临床试验报告称，RAS抑制剂治疗与COVID-19感染或合并症并发症之间没有关联。然而，与COVID-19感染相关的RAS紊乱以及针对该领域的潜在治疗尚未得到解决。在这篇综述中，研究了COVID-19心血管代谢疾病患者中经典RAS失调和反调节RAS活性之间的联系。此外，还讨论了基于ACEI和ARB给药以及ACE-2可用性与COVID-19相关的最新发现，这些发现可能有助于更好地了解RAS对COVID-19病理学的贡献，因为它们在当前的大流行中至关重要。
In the current COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 uses angiotensin-converting enzyme-2 (ACE-2) receptors for cell entry, leading to ACE-2 dysfunction and downregulation, which disturb the balance between the classical and counter-regulatory renin–angiotensin system (RAS) in favor of the classical RAS. RAS dysregulation is one of the major characteristics of several cardiovascular diseases; thus, adjustment of this system is the main therapeutic target. RAS inhibitors—particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs)—are commonly used for treatment of hypertension and cardiovascular disease. Patients with cardiovascular diseases are the group most commonly seen among those with COVID-19 comorbidity. At the beginning of this pandemic, a dilemma occurred regarding the use of ACEIs and ARBs, potentially aggravating cardiovascular and pulmonary dysfunction in COVID-19 patients. Urgent clinical trials from different countries and hospitals reported that there is no association between RAS inhibitor treatment and COVID-19 infection or comorbidity complication. Nevertheless, the disturbance of the RAS that is associated with COVID-19 infection and the potential treatment targeting this area have yet to be resolved. In this review, the link between the dysregulation of classical RAS and counter-regulatory RAS activities in COVID-19 patients with cardiovascular metabolic diseases is investigated. In addition, the latest findings based on ACEI and ARB administration and ACE-2 availability in relation to COVID-19, which may provide a better understanding of the RAS contribution to COVID-19 pathology, are discussed, as they are of the utmost importance amid the current pandemic.