Cardiovascular ACE2 receptor expression in patients undergoing heart transplantation.
Cardiovascular ACE2 receptor expression in patients undergoing heart transplantation.
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DOI：
10.1002/ehf2.13528
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发表时间：
2021-10
影响因子：
3.8
通讯作者：
Sinha S
中科院分区：
文献类型：
--
作者：
Bargehr J;Rericha P;Petchey A;Colzani M;Moule G;Malgapo MC;Rassl D;Tarkin J;Mellor G;Sampaziotis F;Brevini T;Gambardella L;Bennett MR;Sinha S
膜结合血管紧张素转换酶（ACE）2是SARS - CoV - 2的主要细胞接入点，但其在心力衰竭患者中的表达和ACE抑制作用尚未得到定量评估。本研究的目的是表征心脏移植患者心肌和心肌血管中膜结合的ACE2表达，并评估药理学ACE抑制的效果。从36例心脏移植患者的移植心脏中获得左心室组织。在整个队列中，对ACE2与心肌肌钙蛋白T （cTnT）和α‐平滑肌细胞肌动蛋白（SMA）共同注册的抗体进行免疫组织化学染色。在整个心肌和血管中定量评估ACE2受体的表达。ACE2在左室心肌细胞中一致表达（28.3%±22.2%）。ACE2在小口径血管（范围2-9 μm）中也有表达，尽管在定量上水平要低得多（5%±9%的血管）。移植前接受ACE抑制剂治疗的患者与ACE抑制剂阴性对照组的ACE2表达无显著差异（P < 0.05）。作为心脏移植的潜在原因，不同诊断组之间ACE2的表达无显著差异（方差分析0.05）。右心导管测得的N端脑利钠肽（NT‐proBNP） （r2 = 0.37, P = 0.0006）和肺毛细血管楔压（PCWP） （r2 = 0.13, P = 0.043）与心肌细胞中ACE2表达升高显著相关。这些数据提供了心力衰竭患者膜结合心脏ACE2表达的全面表征，ACE抑制剂没有明显的作用。
Membrane‐bound angiotensin‐converting enzyme (ACE)2 is the main cellular access point for SARS‐CoV‐2, but its expression and the effect of ACE inhibition have not been assessed quantitatively in patients with heart failure. The aim of this study was to characterize membrane‐bound ACE2 expression in the myocardium and myocardial vasculature in patients undergoing heart transplantation and to assess the effect of pharmacological ACE inhibition. Left ventricular (LV) tissue was obtained from 36 explanted human hearts from patients undergoing heart transplantation. Immunohistochemical staining with antibodies directed against ACE2 co‐registered with cardiac troponin T (cTnT) and α‐smooth muscle cell actin (SMA) was performed across the entire cohort. ACE2 receptor expression was quantitatively assessed throughout the myocardium and vasculature. ACE2 was consistently expressed throughout the LV myocardium (28.3% ± 22.2% of cardiomyocytes). ACE2 expression was also detected in small calibre blood vessels (range, 2–9 μm), albeit at quantitatively much lower levels (5% ± 9% of blood vessels). There was no significant difference in ACE2 expression between patients receiving ACE inhibitors prior to transplantation and ACE inhibitor‐negative controls (P > 0.05). ACE2 expression did not differ significantly between the different diagnostic groups as the underlying reason for heart transplantation (ANOVA > 0.05). N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) (R 2 = 0.37, P = 0.0006) and pulmonary capillary wedge pressure (PCWP) (R 2 = 0.13, P = 0.043) assessed by right heart catheterization were significantly correlated with greater ACE2 expression in cardiomyocytes. These data provide a comprehensive characterization of membrane‐bound cardiac ACE2 expression in patients with heart failure with no demonstrable effect exerted by ACE inhibitors.
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