Evidence map›Paper›PMID 37640791›Full record

ArticleScientific reports2023

SARS-CoV-2 spike protein induces endothelial inflammation via ACE2 independently of viral replication.

Augusto C Montezano, Livia L Camargo, Sheon Mary, Karla B Neves, Francisco J Rios, Ross Stein, Rheure A Lopes, Wendy Beattie, Jacqueline Thomson, Vanessa Herder and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
11.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 61 citations in OpenAlex.

  1. Trial
  2. Human brain matters: Navigating the neuropathology of COVID-19.Brain pathology (Zurich, Switzerland) · 2026
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  11. Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025
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  18. Review
  19. The peptidoglycan ofScience translational medicine · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Augusto C Montezano *Research Institute of the McGill University Health Centre (RI-MUHC), Site Glen-Block E-Office: E01.3362, 1001, Boul. Decarie, Montreal, QC, H4A3J1, Canada. augusto.montezano@muhc.mcgill.ca.ORCID http://orcid.org/0000-0002-8658-7994
Livia L Camargo *Research Institute of the McGill University Health Centre (RI-MUHC), Site Glen-Block E-Office: E01.3362, 1001, Boul. Decarie, Montreal, QC, H4A3J1, Canada.
Sheon MarySchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Karla B NevesSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Francisco J RiosResearch Institute of the McGill University Health Centre (RI-MUHC), Site Glen-Block E-Office: E01.3362, 1001, Boul. Decarie, Montreal, QC, H4A3J1, Canada.
Ross SteinSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Rheure A LopesSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Wendy BeattieSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Jacqueline ThomsonSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Vanessa HerderMRC Centre for Virus Research, University of Glasgow, Glasgow, UK.
Agnieszka M SzemielMRC Centre for Virus Research, University of Glasgow, Glasgow, UK.
Steven McFarlaneMRC Centre for Virus Research, University of Glasgow, Glasgow, UK.
Massimo PalmariniMRC Centre for Virus Research, University of Glasgow, Glasgow, UK.
Rhian M TouyzResearch Institute of the McGill University Health Centre (RI-MUHC), Site Glen-Block E-Office: E01.3362, 1001, Boul. Decarie, Montreal, QC, H4A3J1, Canada. rhian.touyz@mcgill.ca.ORCID http://orcid.org/0000-0003-0670-0887
University of Glasgow · GBMcGill University Health Centre · CAMRC University of Glasgow Centre for Virus Research · GBUniversity of Strathclyde · GB

Funding

British Heart Foundation CH/12/4/29762British Heart Foundation RE/13/5/30177British Heart Foundation RG/13/7/30099Medical Research Council MC_UU_00034/8Medical Research Council MR/W005611/1Wellcome TrustWellcome Trust 204820/Z/16/ZWellcome Trust 206369/Z/17/Z
6 · The paper itself

Abstract

COVID-19, caused by SARS-CoV-2, is a respiratory disease associated with inflammation and endotheliitis. Mechanisms underling inflammatory processes are unclear, but angiotensin converting enzyme 2 (ACE2), the receptor which binds the spike protein of SARS-CoV-2 may be important. Here we investigated whether spike protein binding to ACE2 induces inflammation in endothelial cells and determined the role of ACE2 in this process. Human endothelial cells were exposed to SARS-CoV-2 spike protein, S1 subunit (rS1p) and pro-inflammatory signaling and inflammatory mediators assessed. ACE2 was modulated pharmacologically and by siRNA. Endothelial cells were also exposed to SARS-CoV-2. rSP1 increased production of IL-6, MCP-1, ICAM-1 and PAI-1, and induced NFkB activation via ACE2 in endothelial cells. rS1p increased microparticle formation, a functional marker of endothelial injury. ACE2 interacting proteins involved in inflammation and RNA biology were identified in rS1p-treated cells. Neither ACE2 expression nor ACE2 enzymatic function were affected by rSP1. Endothelial cells exposed to SARS-CoV-2 virus did not exhibit viral replication. We demonstrate that rSP1 induces endothelial inflammation via ACE2 through processes that are independent of ACE2 enzymatic activity and viral replication. We define a novel role for ACE2 in COVID-19- associated endotheliitis.

Indexed as

COVID-19Endothelial CellsAngiotensin-Converting Enzyme 2HumansInflammationRNA, Double-StrandedSARS-CoV-2Spike Glycoprotein, CoronavirusVirus ReplicationAngiotensin-Converting Enzyme 2RNA, Double-StrandedSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID37640791
PMCPMC10462711
OpenAlexW4386215789

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.