Cardiovascular ACE2 receptor expression in patients undergoing heart transplantation

被引:8
作者
Bargehr, Johannes [1 ,2 ]
Rericha, Patrick [1 ,2 ]
Petchey, Alex [1 ,2 ]
Colzani, Maria [1 ,2 ]
Moule, Georgia [3 ]
Malgapo, Marie Chet [3 ]
Rassl, Doris [3 ]
Tarkin, Jason [2 ]
Mellor, Greg [4 ]
Sampaziotis, Fotis [1 ,5 ]
Brevini, Teresa [1 ]
Gambardella, Laure [1 ,2 ]
Bennett, Martin R. [2 ]
Sinha, Sanjay [1 ,2 ]
机构
[1] Univ Cambridge, Jeffrey Cheah Biomed Ctr, Wellcome MRC Cambridge Stem Cell Inst, Cambridge Biomed Campus,Puddicombe Way, Cambridge CB2 0AW, England
[2] Univ Cambridge, Div Cardiovasc Med, Cambridge, England
[3] Royal Papworth Hosp, Dept Histopathol, Cambridge, England
[4] Royal Papworth Hosp, Cardiol Dept, Cambridge, England
[5] Cambridge Univ Hosp NHS Fdn Trust, Dept Hepatol, Cambridge, England
来源
ESC HEART FAILURE | 2021年 / 8卷 / 05期
基金
英国医学研究理事会; 英国惠康基金;
关键词
COVID-19; SARS-CoV-2; Heart failure; Heart transplantation; ACE inhibitor; SARS-COV-2; INFECTS; ANGIOTENSIN; BLOCKERS; CELLS;
D O I
10.1002/ehf2.13528
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims 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. Methods and results 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 alpha-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 mu m), 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. Conclusions 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.
引用
收藏
页码:4119 / 4129
页数:11
相关论文
共 37 条
  • [1] Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme
    Agata, Jun
    Ura, Nobuyuki
    Yoshida, Hideaki
    Shinshi, Yasuyuki
    Sasaki, Haruki
    Hyakkoku, Masaya
    Taniguchi, Shinya
    Shimamoto, Kazuaki
    [J]. HYPERTENSION RESEARCH, 2006, 29 (11) : 865 - 874
  • [2] COVID-19, Renin-Angiotensin System and Endothelial Dysfunction
    Amraei, Razie
    Rahimi, Nader
    [J]. CELLS, 2020, 9 (07)
  • [3] Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State
    Arentz, Matt
    Yim, Eric
    Klaff, Lindy
    Lokhandwala, Sharukh
    Riedo, Francis X.
    Chong, Maria
    Lee, Melissa
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 323 (16): : 1612 - 1614
  • [4] Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration
    Bargehr, Johannes
    Ong, Lay Ping
    Colzani, Maria
    Davaapil, Hongorzul
    Hofsteen, Peter
    Bhandari, Shiv
    Gambardella, Laure
    Le Novere, Nicolas
    Iyer, Dharini
    Sampaziotis, Fotios
    Weinberger, Florian
    Bertero, Alessandro
    Leonard, Andrea
    Bernard, William G.
    Martinson, Amy
    Figg, Nichola
    Regnier, Michael
    Bennett, Martin R.
    Murry, Charles E.
    Sinha, Sanjay
    [J]. NATURE BIOTECHNOLOGY, 2019, 37 (08) : 895 - +
  • [5] SARS-CoV-2 infects and induces cytotoxic effacts in human cardiomyocytes
    Bojkova, Denisa
    Wagner, Julian U. G.
    Shumliakivska, Mariana
    Aslan, Galip S.
    Saleem, Umber
    Hansen, Arne
    Luxan, Guillermo
    Gunther, Stefan
    Pham, Minh Duc
    Krishnan, Jaya
    Harter, Patrick N.
    Ermel, Utz H.
    Frangakis, Achilleas S.
    Milting, Hendrik
    Zeiher, Andreas M.
    Klingel, Karin
    Cinatl, Jindrich
    Dendorfer, Andreas
    Eschenhagen, Thomas
    Tschoepe, Carsten
    Ciesek, Sandra
    Dimmeler, Stefanie
    [J]. CARDIOVASCULAR RESEARCH, 2020, 116 (14) : 2207 - 2215
  • [6] Marked Up-Regulation of ACE2 in Hearts of Patients With Obstructive Hypertrophic Cardiomyopathy: Implications for SARS-CoV-2-Mediated COVID-19
    Bos, J. Martijn
    Hebl, Virginia B.
    Oberg, Ann L.
    Sun, Zhifu
    Herman, Daniel S.
    Teekakirikul, Polakit
    Seidman, Jonathan G.
    Seidman, Christine E.
    dos Remedios, Cristobal G.
    Maleszewski, Joseph J.
    Schaff, Hartzell, V
    Dearani, Joseph A.
    Noseworthy, Peter A.
    Friedman, Paul A.
    Ommen, Steve R.
    Brozovich, Frank, V
    Ackerman, Michael J.
    [J]. MAYO CLINIC PROCEEDINGS, 2020, 95 (07) : 1354 - 1368
  • [7] Dynamic Regulation of SARS-Cov-2 Binding and Cell Entry Mechanisms in Remodeled Human Ventricular Myocardium
    Bristow, Michael R.
    Zisman, Lawrence S.
    Altman, Natasha L.
    Gilbert, Edward M.
    Lowes, Brian D.
    Minobe, Wayne A.
    Slavov, Dobromir
    Schwisow, Jessica A.
    Rodriguez, Erin M.
    Carroll, Ian A.
    Keuer, Thomas A.
    Buttrick, Peter M.
    Kao, David P.
    [J]. JACC-BASIC TO TRANSLATIONAL SCIENCE, 2020, 5 (09): : 871 - 883
  • [8] The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2
    Chen, Liang
    Li, Xiangjie
    Chen, Mingquan
    Feng, Yi
    Xiong, Chenglong
    [J]. CARDIOVASCULAR RESEARCH, 2020, 116 (06) : 1097 - 1100
  • [9] COVID-19 and Cardiovascular Disease
    Clerkin, Kevin J.
    Fried, Justin A.
    Raikhelkar, Jayant
    Sayer, Gabriel
    Griffin, Jan M.
    Masoumi, Amirali
    Jain, Sneha S.
    Burkhoff, Daniel
    Kumaraiah, Deepa
    Rabbani, LeRoy
    Schwartz, Allan
    Uriel, Nir
    [J]. CIRCULATION, 2020, 141 (20) : 1648 - 1655
  • [10] A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9
    Donoghue, M
    Hsieh, F
    Baronas, E
    Godbout, K
    Gosselin, M
    Stagliano, N
    Donovan, M
    Woolf, B
    Robison, K
    Jeyaseelan, R
    Breitbart, RE
    Acton, S
    [J]. CIRCULATION RESEARCH, 2000, 87 (05) : E1 - E9