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http://purl.uniprot.org/citations/34807265http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34807265http://www.w3.org/2000/01/rdf-schema#comment"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."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.org/dc/terms/identifier"doi:10.1042/cs20210735"xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Davidson A.D."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Hill D."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Gupta K."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Elvers K.T."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Arnold D."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Berger I."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Caputo M."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Gillespie K."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Avolio E."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Milligan R."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Madeddu P."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Gamez M."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Carrabba M."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Foster R.R."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Beltrami A.P."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Kavanagh Williamson M."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/author"Hamilton F."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/name"Clin Sci (Lond)"xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/pages"2667-2689"xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/title"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."xsd:string
http://purl.uniprot.org/citations/34807265http://purl.uniprot.org/core/volume"135"xsd:string
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