Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China,
Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany,
Kidney Blood Press Res. 2022;47(9):565-575. doi: 10.1159/000525368. Epub 2022 Jul 25.
The angiotensin-converting enzyme 2 (ACE2) as well as the transmembrane protease serine type 2 (TMPRSS2) have been found to play roles in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection risk and severity of COVID-19 might be indicated by the expression of ACE2 and TMPRSS2 in the lung.
A high-salt diet rat model and renin-angiotensin-aldosterone system (RAAS) blockade were used to test whether these factors affect ACE2 and TMPRSS2 expression in the lung. A normal (0.3% NaCl), a medium (2% NaCl), or a high (8% NaCl) salt diet was fed to rats for 12 weeks, along with enalapril or telmisartan, before examining the lung for histopathological alteration. Using immunofluorescence and qRT-PCR, the localization as well as mRNA expression of ACE2 and TMPRSS2 were investigated.
The findings provide evidence that both TMPRSS2 and ACE2 are highly expressed in bronchial epithelial cells as well as ACE2 was also expressed in alveolar type 2 cells. High-salt diet exposure in rats leads to elevated ACE2 expression on protein level. Treatment with RAAS blockers had no effect on lung tissue expression of ACE2 and TMPRSS2.
These findings offer biological support regarding the safety of these drugs that are often prescribed to COVID-19 patients with cardiovascular comorbidity. High salt intake, on the other hand, might adversely affect COVID-19 outcome. Our preclinical data should stimulate clinical studies addressing this point of concern.
血管紧张素转换酶 2（ACE2）和跨膜丝氨酸蛋白酶 2（TMPRSS2）已被发现可参与严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的细胞进入，该病毒可引起 2019 年冠状病毒病（COVID-19）。SARS-CoV-2 感染风险和 COVID-19 的严重程度可能由肺中 ACE2 和 TMPRSS2 的表达所指示。
使用高盐饮食大鼠模型和肾素-血管紧张素-醛固酮系统（RAAS）阻断来测试这些因素是否会影响肺中的 ACE2 和 TMPRSS2 表达。给大鼠喂食正常（0.3%NaCl）、中盐（2%NaCl）或高盐（8%NaCl）饮食 12 周，然后用依那普利或替米沙坦进行治疗，再检查肺组织的组织病理学改变。通过免疫荧光和 qRT-PCR 检测 ACE2 和 TMPRSS2 的定位和 mRNA 表达。
研究结果提供了证据表明，TMPRSS2 和 ACE2 在支气管上皮细胞中均高度表达，并且 ACE2 也在肺泡 2 型细胞中表达。高盐饮食暴露会导致大鼠肺组织 ACE2 蛋白水平表达升高。RAAS 阻滞剂治疗对肺组织 ACE2 和 TMPRSS2 的表达无影响。
这些发现为经常开给 COVID-19 合并心血管合并症患者的这些药物的安全性提供了生物学支持。另一方面，高盐摄入可能对 COVID-19 结局产生不利影响。我们的临床前数据应激发针对这一关注点的临床研究。
