ArticleClinical science (London, England : 1979)2021
The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease.
Article in Clinical science (London, England : 1979), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 96 papers, 3 of them syntheses that pooled it.
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Who cites it
96 citing papers in PubMed, 3 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- An integrative meta-analysis of SARS-CoV-2 RNA-protein interactomes identifies conserved host factors shared with other RNA viruses.Briefings in functional genomics · 2026Pooled it
- Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis.ESC heart failure · 2025Pooled it
- Single-cell analysis of adult human heart across healthy and cardiovascular disease patients reveals the cellular landscape underlying SARS-CoV-2 invasion of myocardial tissue through ACE2.Journal of translational medicine · 2023Pooled it
- Beyond correlation and causation: epistemic caution, anomalous findings, and COVID-19 vaccine safety.Philosophy, ethics, and humanities in medicine : PEHM · 2026Review
- Spike 1 protein of SARS-CoV-2 induces endothelial inflammation and vascular dysfunction through interferon ISG15-dependent mechanisms.Cardiovascular research · 2026Article
- Neurological impairment in long COVID: implications for neurodegenerative disease.Journal of translational medicine · 2026Review
- Etiology Model of Kawasaki Disease and Multisystem Inflammatory Syndromes: Mast Cell Activation.Current issues in molecular biology · 2026Article
- SARS-CoV-2 spike protein can bind fibrin(ogen), but does not alter plasma fibrin formation, clot structure, or lysis.Blood advances · 2026Article
- "Bridging the clinical, molecular and genetic perspectives on myocarditis in post-COVID-19 era".International journal of cardiology. Cardiovascular risk and prevention · 2026Review
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- Unique Features and Collateral Immune Effects of mRNA-LNP COVID-19 Vaccines: Plausible Mechanisms of Adverse Events and Complications.Pharmaceutics · 2025Review
- SARS-CoV-2 spike protein-induced inflammation underlies proarrhythmia in COVID-19.Scientific reports · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- Multisystem Endothelial Inflammation: A Key Driver of Adverse Events Following mRNA-Containing COVID-19 Vaccines.Vaccines · 2025Review
- Review
- The Possible Mechanistic Basis of Individual Susceptibility to Spike Protein Injury.Advances in virology · 2025Review
- Soluble SARS-CoV-2 Spike glycoprotein: considering some potential pathogenic effects.Frontiers in immunology · 2025Review
- Risk impact of SARS-CoV-2 coronavirus and spike protein on cardiac tissue: a comprehensive review.Physiological research · 2024Review
- Pulmonary Artery Vasa Vasorum Damage in Severe COVID-19-Induced Pulmonary Fibrosis.Annals of thoracic surgery short reports · 2024Article
- Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3 Inflammasomes and NF-κB Signaling.Cells · 2024Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a broad range of clinical responses including prominent microvascular damage. The capacity of SARS-CoV-2 to infect vascular cells is still debated. Additionally, the SARS-CoV-2 Spike (S) protein may act as a ligand to induce non-infective cellular stress. We tested this hypothesis in pericytes (PCs), which are reportedly reduced in the heart of patients with severe coronavirus disease-2019 (COVID-19). Here we newly show that the in vitro exposure of primary human cardiac PCs to the SARS-CoV-2 wildtype strain or the α and δ variants caused rare infection events. Exposure to the recombinant S protein alone elicited signalling and functional alterations, including: (1) increased migration, (2) reduced ability to support endothelial cell (EC) network formation on Matrigel, (3) secretion of pro-inflammatory molecules typically involved in the cytokine storm, and (4) production of pro-apoptotic factors causing EC death. Next, adopting a blocking strategy against the S protein receptors angiotensin-converting enzyme 2 (ACE2) and CD147, we discovered that the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in PCs. The neutralisation of CD147, either using a blocking antibody or mRNA silencing, reduced ERK1/2 activation, and rescued PC function in the presence of the S protein. Immunoreactive S protein was detected in the peripheral blood of infected patients. In conclusion, our findings suggest that the S protein may prompt PC dysfunction, potentially contributing to microvascular injury. This mechanism may have clinical and therapeutic implications.
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Registered trials
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.