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培哚普利降低暴露于严重急性呼吸综合征冠状病毒2(SARS-CoV-2)S1刺突蛋白的人脂肪细胞中血管紧张素转换酶2(ACE2)的表达。

Perindopril decreases angiotensin-converting enzyme 2 (ACE2) expression in human adipocytes exposed to SARS-CoV-2 S1 spike protein.

作者信息

Harsoyo Primasitha M, Ardiana Meity, Hermawan Hanestya O, Purnamasari Yeni, Anandita Faizal A

机构信息

Department of Cardiology and Vascular Medicine, Faculty of Medical, Universitas Airlangga, Surabaya, Indonesia.

Department of Cardiology and Vascular Medicine, Dr. Soetomo General Hospital, Surabaya, Indonesia.

出版信息

Narra J. 2024 Aug;4(2):e746. doi: 10.52225/narra.v4i2.746. Epub 2024 May 2.

Abstract

The expression of angiotensin-converting enzyme 2 (ACE2) in the adipose tissues of obese patients needs further study, as it may aid infection and serve as a viral reservoir. There has been controversy over whether to use ACE inhibitors to prevent coronavirus disease 2019 (COVID-19) severity. Perindopril, an ACE2 inhibitor, has been proposed; however, its relationship with COVID-19 has not yet been clear. The aim of this study was to investigate the effect of perindopril to reduce the expression of ACE2 and pro-inflammatory cytokine in adipocytes exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Enzymatic isolation of adipose tissues was performed from obese male donor patients aged 30-50 years, then exposed it with SARS-CoV-2 S1 spike protein. This study also included human recombinant ACE2 (hrsACE2) as a comparison to perindopril. The expression of ACE2 was evaluated using ELISA. Our data indicated that SARS-CoV-2 Spike protein exposure increased ACE2 expression significantly. Administration of perindopril decreased ACE2 expression (43.37 μg/mL) significantly compared to the positive group (80.31 μg/mL) (<0.001). Perindopril administration also decreased IL-6 levels significantly compared to positive group (<0.001). This study highlights that perindopril could reduce the ACE2 expression and pro-inflammatory cytokine levels in adipocytes exposed to SARS-CoV-2 S1 spike protein.

摘要

肥胖患者脂肪组织中血管紧张素转换酶2(ACE2)的表达需要进一步研究,因为它可能有助于感染并充当病毒库。对于是否使用血管紧张素转换酶抑制剂来预防2019冠状病毒病(COVID-19)的严重程度一直存在争议。有人提出使用培哚普利这种血管紧张素转换酶2抑制剂;然而,其与COVID-19的关系尚不清楚。本研究的目的是调查培哚普利对降低暴露于严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的脂肪细胞中ACE2和促炎细胞因子表达的影响。从30至50岁的肥胖男性供体患者身上进行脂肪组织的酶解分离,然后用SARS-CoV-2 S1刺突蛋白处理。本研究还纳入了人重组ACE2(hrsACE2)作为与培哚普利的对照。使用酶联免疫吸附测定法(ELISA)评估ACE2的表达。我们的数据表明,暴露于SARS-CoV-2刺突蛋白会显著增加ACE2的表达。与阳性组(80.31μg/mL)相比,培哚普利给药显著降低了ACE2的表达(43.37μg/mL)(<0.001)。与阳性组相比,培哚普利给药也显著降低了白细胞介素-6水平(<0.001)。本研究强调,培哚普利可以降低暴露于SARS-CoV-2 S1刺突蛋白的脂肪细胞中ACE2的表达和促炎细胞因子水平。

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