Dysbalance of ACE2 levels - a possible cause for severe COVID-19 outcome in COPD.
Dysbalance of ACE2 levels - a possible cause for severe COVID-19 outcome in COPD.
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ACE 2水平失衡-COPD患者严重COVID-19结局的可能原因
DOI：
10.1002/cjp2.224
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Kwapiszewska G
中科院分区：
文献类型：
--
作者：
Fließer E;Birnhuber A;Marsh LM;Gschwandtner E;Klepetko W;Olschewski H;Kwapiszewska G
严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）对全球医疗系统构成严重威胁。病毒与血管紧张素转换酶2（ACE 2）的结合是感染机制中的重要步骤。然而，尚不清楚慢性肺病（CLD）患者（如慢性阻塞性肺病（COPD）、特发性肺动脉高压（IPAH）或肺纤维化（PF））中ACE 2的表达与对照组相比是否发生变化。我们使用COPD（n = 28）、IPAH（n = 10）和PF（n = 10）患者的肺样本以及健康对照供体（n = 10）组织样本，研究ACE 2和可能影响SARS-CoV-2感染过程的相关辅因子的表达。通过定量PCR和开放获取RNA测序数据集测定ACE 2受体、推定受体CD 147/BSG和病毒进入辅因子TMPRSS 2（跨膜丝氨酸蛋白酶2）、EZR和FURIN的表达水平。免疫组织化学和单细胞RNA测序（scRNAseq）分析分别用于定位和共表达。通过酶联免疫吸附试验分析可溶性ACE 2（sACE 2）血浆水平。与供体、IPAH和PF肺组织相比，COPD中ACE 2、TMPRSS 2和EZR的基因表达显著升高，但与健康对照和IPAH血浆样品相比，COPD和PF血浆中循环sACE 2水平显著降低。COPD患者肺组织FURIN和CD 147/BSG表达下调。这些变化均与肺血流动力学变化无关。组织学分析显示ACE 2、TMPRSS 2和Ezrin在支气管区域和上皮细胞中共表达。这通过scRNAseq分析证实。与对照组相比，IPAH和特发性PF的肺组织中所分析的分子的表达没有显著变化。总之，我们发现COPD患者肺组织中ACE 2和TMPRSS 2表达增加，同时保护性sACE 2减少。这些变化代表了COPD患者对SARS-CoV-2感染易感性增加的可能风险因素。
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses a serious threat to healthcare systems worldwide. Binding of the virus to angiotensin‐converting enzyme 2 (ACE2) is an important step in the infection mechanism. However, it is unknown if ACE2 expression in patients with chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary arterial hypertension (IPAH), or pulmonary fibrosis (PF), is changed as compared to controls. We used lung samples from patients with COPD (n = 28), IPAH (n = 10), and PF (n = 10) as well as healthy control donor (n = 10) tissue samples to investigate the expression of ACE2 and related cofactors that might influence the course of SARS‐CoV‐2 infection. Expression levels of the ACE2 receptor, the putative receptor CD147/BSG, and the viral entry cofactors TMPRSS2 (transmembrane serine protease 2), EZR, and FURIN were determined by quantitative PCR and in open‐access RNA sequencing datasets. Immunohistochemical and single‐cell RNA sequencing (scRNAseq) analyses were used for localization and coexpression, respectively. Soluble ACE2 (sACE2) plasma levels were analyzed by enzyme‐linked immunosorbent assay. In COPD as compared to donor, IPAH, and PF lung tissue, gene expression of ACE2, TMPRSS2, and EZR was significantly elevated, but circulating sACE2 levels were significantly reduced in COPD and PF plasma compared to healthy control and IPAH plasma samples. Lung tissue expressions of FURIN and CD147/BSG were downregulated in COPD. None of these changes were associated with changes in pulmonary hemodynamics. Histological analysis revealed coexpression of ACE2, TMPRSS2, and Ezrin in bronchial regions and epithelial cells. This was confirmed by scRNAseq analysis. There were no significant expression changes of the analyzed molecules in the lung tissue of IPAH and idiopathic PF as compared to control. In conclusion, we reveal increased ACE2 and TMPRSS2 expression in lung tissue with a concomitant decrease of protective sACE2 in COPD patients. These changes represent the possible risk factors for an increased susceptibility of COPD patients to SARS‐CoV‐2 infection.
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