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HomeCirculation ResearchVol. 128, No. 9SARS-CoV-2 Spike Protein
Impairs Endothelial Function via Downregulation of ACE 2
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SARS-CoV-2 Spike Protein Impairs Endothelial Function via
Downregulation of ACE 2

  * Yuyang Lei,
  * Jiao Zhang,
  * Cara R. Schiavon,
  * Ming He,
  * Lili Chen,
  * Hui Shen,
  * Yichi Zhang,
  * Qian Yin,
  * Yoshitake Cho,
  * Leonardo Andrade,
  * Gerald S. Shadel,
  * Mark Hepokoski,
  * Ting Lei,
  * Hongliang Wang,
  * Jin Zhang,
  * Jason X.-J. Yuan,
  * Atul Malhotra,
  * Uri Manor,
  * Shengpeng Wang,
  * Zu-Yi Yuan,
  * John Y-J. Shyy

Yuyang Lei
Yuyang Lei

Cardiology, First Affiliated Hospital of Xi'an Jiaotong University
(Y.L., Jiao Zhang, Z.-Y.Y.).

Cardiovascular Research Center, School of Basic Medical Sciences
(Y.L., Jiao Zhang, L.C., Q.Y., S.W.).

+U. Manor, S. Wang, Z.-Y. Yuan, and J.Y.-J. Shyy contributed equally
as senior authors.

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,
Jiao Zhang
Jiao Zhang

Cardiology, First Affiliated Hospital of Xi'an Jiaotong University
(Y.L., Jiao Zhang, Z.-Y.Y.).

Cardiovascular Research Center, School of Basic Medical Sciences
(Y.L., Jiao Zhang, L.C., Q.Y., S.W.).

Xi'an Jiaotong University Health Science Center. Cardiology,
Department of Medicine (Jiao Zhang, M. He, H.S., Y.Z., Y.C.,
J.Y.-J.S.), University of California, San Diego, La Jolla, CA.

+U. Manor, S. Wang, Z.-Y. Yuan, and J.Y.-J. Shyy contributed equally
as senior authors.

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,
Cara R. Schiavon
Cara R. Schiavon

https://orcid.org/0000-0002-9311-2145

Waitt Advanced Biophotonics Center (C.R.S., L.A., U.M.).

Molecular and Cellular Biology Laboratory, Salk Institute for
Biological Studies, La Jolla, CA (C.R.S., G.S.S.).

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,
Ming He
Ming He

Xi'an Jiaotong University Health Science Center. Cardiology,
Department of Medicine (Jiao Zhang, M. He, H.S., Y.Z., Y.C.,
J.Y.-J.S.), University of California, San Diego, La Jolla, CA.

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,
Lili Chen
Lili Chen

Cardiovascular Research Center, School of Basic Medical Sciences
(Y.L., Jiao Zhang, L.C., Q.Y., S.W.).

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,
Hui Shen
Hui Shen

Xi'an Jiaotong University Health Science Center. Cardiology,
Department of Medicine (Jiao Zhang, M. He, H.S., Y.Z., Y.C.,
J.Y.-J.S.), University of California, San Diego, La Jolla, CA.

Cardiology, the Affiliated Hospital of Yangzhou University (H.S.).

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,
Yichi Zhang
Yichi Zhang

Xi'an Jiaotong University Health Science Center. Cardiology,
Department of Medicine (Jiao Zhang, M. He, H.S., Y.Z., Y.C.,
J.Y.-J.S.), University of California, San Diego, La Jolla, CA.

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,
Qian Yin
Qian Yin

Cardiovascular Research Center, School of Basic Medical Sciences
(Y.L., Jiao Zhang, L.C., Q.Y., S.W.).

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,
Yoshitake Cho
Yoshitake Cho

Xi'an Jiaotong University Health Science Center. Cardiology,
Department of Medicine (Jiao Zhang, M. He, H.S., Y.Z., Y.C.,
J.Y.-J.S.), University of California, San Diego, La Jolla, CA.

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,
Leonardo Andrade
Leonardo Andrade

Waitt Advanced Biophotonics Center (C.R.S., L.A., U.M.).

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,
Gerald S. Shadel
Gerald S. Shadel

Molecular and Cellular Biology Laboratory, Salk Institute for
Biological Studies, La Jolla, CA (C.R.S., G.S.S.).

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,
Mark Hepokoski
Mark Hepokoski

Pulmonary, Critical Care and Sleep Medicine, Department of Medicine
(M. Hepokoski, J.X.-J.Y., A.M.), University of California, San Diego,
La Jolla, CA.

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,
Ting Lei
Ting Lei

Pathology, School of Basic Medical Sciences (T.L.), University of
California, San Diego, La Jolla, CA.

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,
Hongliang Wang
Hongliang Wang

Pathogen Biology and Immunology, School of Basic Medical Sciences
(H.W.), University of California, San Diego, La Jolla, CA.

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,
Jin Zhang
Jin Zhang

Pharmacology (Jin Zhang), University of California, San Diego, La
Jolla, CA.

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,
Jason X.-J. Yuan
Jason X.-J. Yuan

Pulmonary, Critical Care and Sleep Medicine, Department of Medicine
(M. Hepokoski, J.X.-J.Y., A.M.), University of California, San Diego,
La Jolla, CA.

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,
Atul Malhotra
Atul Malhotra

Pulmonary, Critical Care and Sleep Medicine, Department of Medicine
(M. Hepokoski, J.X.-J.Y., A.M.), University of California, San Diego,
La Jolla, CA.

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,
Uri Manor
Uri Manor

https://orcid.org/0000-0002-9802-1955

Waitt Advanced Biophotonics Center (C.R.S., L.A., U.M.).

For Sources of Funding and Disclosures, see page 1324.

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,
Shengpeng Wang
Shengpeng Wang

Cardiovascular Research Center, School of Basic Medical Sciences
(Y.L., Jiao Zhang, L.C., Q.Y., S.W.).

For Sources of Funding and Disclosures, see page 1324.

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,
Zu-Yi Yuan
Zu-Yi Yuan

Zu-Yi Yuan, MD, PhD, Department of Cardiology, First Affiliated
Hospital of Xi'an Jiaotong University, 277 Yanta W Rd, Xi'an 710061,
China, Email

E-mail Address: [email protected]

Cardiology, First Affiliated Hospital of Xi'an Jiaotong University
(Y.L., Jiao Zhang, Z.-Y.Y.).

For Sources of Funding and Disclosures, see page 1324.

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,
John Y-J. Shyy
John Y-J. Shyy

Correspondence to: John Y-J. Shyy, PhD, Division of Cardiology,
Department of Medicine, University of California, San Diego, 9500
Gilman Dr, La Jolla, CA 92093, Email

E-mail Address: [email protected]

https://orcid.org/0000-0002-5625-753X

Xi'an Jiaotong University Health Science Center. Cardiology,
Department of Medicine (Jiao Zhang, M. He, H.S., Y.Z., Y.C.,
J.Y.-J.S.), University of California, San Diego, La Jolla, CA.

For Sources of Funding and Disclosures, see page 1324.

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Originally published31 Mar 2021https://doi.org/10.1161/
CIRCRESAHA.121.318902Circulation Research. 2021;128:1323-1326

  * is related to
      + Meet the First Authors

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Footnotes

*Y. Lei and J. Zhang contributed equally.

+U. Manor, S. Wang, Z.-Y. Yuan, and J.Y.-J. Shyy contributed equally
as senior authors.

For Sources of Funding and Disclosures, see page 1324.

Correspondence to: John Y-J. Shyy, PhD, Division of Cardiology,
Department of Medicine, University of California, San Diego, 9500
Gilman Dr, La Jolla, CA 92093, Email [email protected]ucsd.edu
Zu-Yi Yuan, MD, PhD, Department of Cardiology, First Affiliated
Hospital of Xi'an Jiaotong University, 277 Yanta W Rd, Xi'an 710061,
China, Email [email protected]xjtu.edu.cn

References

  * 1. Teuwen LA, Geldhof V, Pasut A, Carmeliet P. COVID-19: the
    vasculature unleashed.Nat Rev Immunol. 2020; 20:389-391. doi:
    10.1038/s41577-020-0343-0Google Scholar
  * 2. Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP,
    Virgilio-da-Silva JV, Prodonoff JS, Carregari VC, de Biagi Junior
    CAO, Crunfli F, et al.. Elevated glucose levels favor SARS-CoV-2
    infection and monocyte response through a HIF-1a/
    glycolysis-dependent axis.Cell Metab. 2020; 32:437-446.e5. doi:
    10.1016/j.cmet.2020.07.007Google Scholar
  * 3. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P,
    Zhang Y, Deng W, et al.. A crucial role of angiotensin converting
    enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.Nat Med. 
    2005; 11:875-879. doi: 10.1038/nm1267Google Scholar
  * 4. Shen H, Zhang J, Wang C, Jain PP, Xiong M, Shi X, Lei Y, Chen
    S, Yin Q, Thistlethwaite PA, et al.. MDM2-Mediated Ubiquitination
    of angiotensin-converting enzyme 2 contributes to the development
    of pulmonary arterial hypertension.Circulation. 2020;
    142:1190-1204. doi: 10.1161/CIRCULATIONAHA.120.048191Google
    Scholar
  * 5. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R,
    Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. 
    Endothelial cell infection and endotheliitis in COVID-19.Lancet. 
    2020; 395:1417-1418. doi: 10.1016/S0140-6736(20)30937-5Google
    Scholar

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        Circulation Research. 2021;128:1238-1239
  * 

Circulation Research, volume 128 issue 9 cover
April 30, 2021
Vol 128, Issue 9

Article Information

Metrics

Download: 186

  * (c) 2021 American Heart Association, Inc.

https://doi.org/10.1161/CIRCRESAHA.121.318902

PMID: 33784827

  * Originally published3/31/21 2:00 AM

Keywords

  * SARS-CoV-2
  * angiotensin-converting enzyme 2
  * endothelium

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Circulation Research

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