The effect of renin-angiotensin-aldosterone system inhibitors on organ-specific ace2 expression in zebrafish and its implications for COVID-19.
The effect of renin-angiotensin-aldosterone system inhibitors on organ-specific ace2 expression in zebrafish and its implications for COVID-19.
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DOI：
10.1038/s41598-021-03244-5
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发表时间：
2021-12-08
影响因子：
4.6
通讯作者：
Guo S
中科院分区：
文献类型：
--
作者：
Kim GJ;Melgoza A;Jiang F;Guo S
在导致严重疾病或死亡的SARS-CoV-2感染病例中，许多人有预先存在的疾病，如高血压，并服用肾素-血管紧张素-醛固酮系统（RAAS）抑制剂。血管紧张素转换酶-2（ACE 2）是RAAS途径的关键蛋白，也介导SARS-CoV-2进入细胞。RAAS抑制剂可能会影响ace 2的表达水平，从而影响患者对SARS-CoV-2的易感性。然而，目前缺乏多器官特异性信息，除啮齿动物外，没有其他物种被检查过。为了解决这一知识缺口，我们用RAAS抑制剂阿利吉仑、奥美沙坦和卡托普利连续7天处理成年斑马鱼，并对脑、鳃、心脏、肠、肾和肝中的主要RAAS途径基因进行qRT-PCR分析。奥美沙坦和卡托普利均显著增加心脏、鳃和肾脏ace 2的表达。奥美沙坦也增加肠内ace 2的表达。相反，阿利吉仑显著降低心脏中ace 2的表达。停止化合物治疗7天并不能使ace 2表达恢复到基线水平。虽然抗高血压RAAS抑制剂对人类SARS-CoV-2感染的潜在风险或益处仍不确定，但这项研究提供了关于RAAS抑制剂对另一种脊椎动物模型中器官特异性ace 2表达的影响的新见解，从而为未来在COVID-19背景下使用RAAS抑制剂的临床决策提供了比较数据并奠定了科学基础。
Among cases of SARS-CoV-2 infections that result in serious conditions or death, many have pre-existing conditions such as hypertension and are on renin–angiotensin–aldosterone system (RAAS) inhibitors. The angiotensin-converting-enzyme-2 (ACE2), a key protein of the RAAS pathway, also mediates cellular entry of SARS-CoV-2. RAAS inhibitors might affect the expression levels of ace2, which could impact patient susceptibility to SARS-CoV-2. However, multi-organ-specific information is currently lacking and no species other than rodents have been examined. To address this knowledge gap, we treated adult zebrafish with the RAAS inhibitors aliskiren, olmesartan, and captopril for 7 consecutive days and performed qRT-PCR analysis of major RAAS pathway genes in the brain, gill, heart, intestine, kidney, and liver. Both olmesartan and captopril significantly increased ace2 expression in the heart, gill, and kidney. Olmesartan also increased ace2 expression in the intestine. Conversely, aliskiren significantly decreased ace2 expression in the heart. Discontinuation of compound treatments for 7 days did not return ace2 expression to baseline levels. While potential risks or benefits of antihypertensive RAAS inhibitors to SARS-CoV-2 infections in humans remain uncertain, this study provides new insights regarding the impact of RAAS inhibitors on organ-specific ace2 expression in another vertebrate model, thereby providing comparative data and laying scientific groundwork for future clinical decisions of RAAS inhibitor use in the context of COVID-19.
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