Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Senescent endothelial cells are predisposed to SARS-CoV-2 infection and subsequent endothelial dysfunction

ABSTRACT: The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains to spread worldwide. COVID-19 is characterized by the striking high mortality in elderly; however, its mechanistic insights remain unclear. Systemic thrombosis has been highlighted in the pathogenesis of COVID-19, and lung microangiopathy in association with endothelial cells (ECs) injury has been reported by post-mortem analysis of the lungs. Here, we experimentally investigated the SARS-CoV-2 infection in cultured human ECs, and performed a comparative analysis for post-infection molecular events using early passage and replicative senescent ECs. We found that; 1) SARS-CoV-2 infects ECs but does not replicate and disappears in 72 hours without causing severe cell damage, 2) Senescent ECs are highly susceptible to SARS-CoV-2 infection, 3) SARS-CoV-2 infection alters various genes expression, which could cause EC dysfunctions, 4) More genes expression is affected in senescent ECs by SARS-CoV-2 infection than in early passage ECs, which might causes further exacerbated dysfunction in senescent ECs. These data suggest that sustained EC dysfunctions due to SARS-CoV-2 infection may contribute to the microangiopathy in the lungs, leading to deteriorated inflammation and thrombosis in COVID-19. Our data also suggest a possible causative role of EC senescence in the aggravated disease in elder COVID-19 patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206677 | GEO | 2023/05/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Human cardiac pericytes are susceptible to SARS-CoV-2 infection

Project description:Coronavirus disease 2019 (COVID-19) is associated with serious cardiovascular complications, including myocarditis, thrombosis, and dysregulated hemodynamic responses. The mechanism(s) underlying these disease manifestations are incompletely understood. Given a critical role for pericytes in supporting endothelial cell health and maintaining vascular integrity, we hypothesized that infection of pericytes could explain some of the cardiovascular complications of COVID-19. Here, we present evidence of SARS-CoV-2 infection in cardiac pericytes in patients with COVID-19 myocarditis. We show that cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. SARS-CoV-2 enters cardiac pericytes through an ACE2 and endosomal-dependent mechanism. Consequences of cardiac pericyte infection include upregulation of inflammatory chemokine and cytokine expression, type I interferon signaling, mediators of endothelial constriction, and cell death. Collectively, these data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a possible role for pericyte infection in the pathogenesis of COVID-19.

2022-08-31 | GSE183850 | GEO

The SARS-CoV-2 Spike protein modifies the transcriptional profile of human cardiac pericytes

Project description:Human cardiac pericytes express the receptors for SARS-CoV-2 and contribute to microvascular dysfunction in COVID-19 patients. The SARS-CoV-2 capsid Spike protein seems to play a direct role in COVID-19 microangiopathy, but it is not known yet whether the Spike protein alone, without the infectious virus, can induce transcriptional alterations in pericytes. This study investigated the signalling pathways activated by the Spike protein in cultured human cardiac pericytes. We found that 309 RNA transcripts were significantly modulated in pericytes exposed to the Spike protein, with the upregulation of pathways linked to inflammation and viral infection.

2023-05-09 | GSE218644 | GEO

Linear epitope-specific IgG responses to SARS-CoV-2 and related human coronaviruses in human COVID-19 convalescent sera

Project description:The on-going COVID-19 pandemic requires a deeper understanding of the long-term antibody responses that persist following SARS-CoV-2 infection. To that end, we determined epitope-specific IgG antibody responses in COVID-19 convalescent sera collected at 5 months post-diagnosis and compared that to sera from naïve individuals. Each serum sample was reacted with a high-density peptide microarray representing the complete proteome of SARS-CoV-2 as 15 mer peptides with 11 amino acid overlap and homologs of spike glycoprotein, nucleoprotein, membrane protein, and envelope small membrane protein from related human coronaviruses. Binding signatures were compared between COVID-19 convalescent patients and naïve individuals using the web service tool EPIphany.

2022-02-05 | E-MTAB-10740 | biostudies-arrayexpress

Absence of COVID-19-associated Changes in Coagulation and Thrombosis in the Ferret Model

Project description:Many patients who are diagnosed with coronavirus disease 2019 (COVID-19) suffer from venous thromboembolic complications despite the use of stringent anticoagulant prophylaxis. Studies on the exact mechanism(s) underlying thrombosis in COVID-19 are limited as animal models commonly used to study venous thrombosis pathophysiology (i.e. rats and mice) are naturally not susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Ferrets are susceptible to SARS-CoV-2 infection, successfully used to study virus transmission, and were previously used to study activation of coagulation and thrombosis during influenza virus infection. Here, we used plasma and lung material from SARS-CoV-2-inoculated ferrets to explore their use in studying COVID-19-associated changes in coagulation and thrombosis. Lungs of ferrets inoculated intranasally with SARS-CoV-2 demonstrated alveolar septa that were mildly expanded by macrophages, and diffuse interstitial histiocytic pneumonia. However, no macroscopical or microscopical evidence of vascular thrombosis in the lungs of SARS-CoV-2-inoculated ferrets was found. Longitudinal plasma profiling using a mass spectrometry-based approach revealed minor differences in plasma protein profiles in SARS-CoV-2-inoculated ferrets up to 2 weeks post-infection. Apart from fibrinogen, the majority of plasma coagulation factors were stable and demonstrated a low coefficient of variation. We conclude that while ferrets are an essential and well-suited animal model to study SARS-CoV-2 transmission, their use to study SARS-CoV-2-related changes relevant to thrombotic disease is limited.

2022-07-19 | PXD027582 | Pride

High titers and low fucosylation of early anti-SARS-CoV-2 IgG promote hyper-inflammation by anti-inflammatory macrophages (MIL10)

Project description:Patients diagnosed with coronavirus disease 2019 (COVID-19) mostly become critically ill around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific IgG in serum of critically ill COVID-19 patients induces hyper-inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19. First, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease. Second, we found that anti-spike IgG from patients with severe COVID-19 is intrinsically more pro-inflammatory because of different glycosylation, particularly low fucosylation, of the Fc tail. Notably, low anti-spike IgG fucosylation normalized in a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. We identified Fcγ Receptor (FcγR) IIa and FcγRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19-associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, we show that anti-spike IgG-activated macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Finally, we demonstrate that the hyper-inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of the kinase, Syk.

2021-04-30 | E-MTAB-10431 | biostudies-arrayexpress

Transcriptome profiling of lungs from young and aged hamster

Project description:Older age is one of the strongest risk factors for COVID-19 morbidity and mortality. Here, we sought to determine whether age-associated cellular senescence contributes to the severity of COVID-19 by studying the well-established golden hamster model of SARS-CoV-2-driven lung disease. We found that aged hamsters (22 months of age) accumulate senescent cells in the lungs and that the senolytic drug ABT-263 depletes these cells at baseline and during a SARS-CoV-2 infection. Relative to young hamsters (2 months of age), aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Interestingly, early treatment with ABT-263 was associated with a significantly lower pulmonary viral load, an effect associated with lower angiotensin converting enzyme 2, the receptor for SARS-CoV-2, and an amelioration of COVID-19-like lung disease in aged (but not young) animals. ABT-263 treatment of aged animals was also associated with lower pulmonary and systemic levels of senescence-associated secretory phenotype factors. Furthermore, early removal of senescent cells reduced the longer-term pulmonary inflammation. These data demonstrate the causative role of age-associated pre-existing senescent cells on the pathologic severity of experimental COVID-19.

2023-04-30 | GSE230301 | GEO

Vascular Disease and Thrombosis in SARS-CoV-2 Infected Humans and Rhesus Macaques

Project description:The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details that underlie these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular and cellular pathways associated with SARS-CoV-2 pathogenesis, we performed transcriptomic analyses of bronchoalveolar lavage (BAL) samples and peripheral blood, and proteomics analyses of serum from infected rhesus macaques. We observed upregulation of macrophage signatures, complement cascade pathways, platelet activation, and markers of thrombosis in BAL and peripheral blood as well as extensive macrophage infiltrates in lung. These observations coincided with robust induction of interferon and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFa and NF-κB as well as downstream signaling pathways. These findings suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2 induced vascular disease. Our findings also suggest potential novel therapeutic targets for COVID-19 disease.

2020-10-20 | GSE156701 | GEO

Characterisation of the blood RNA host response underpinning severity in COVID-19 patients

Project description:Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA-Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups.

2022-07-19 | E-MTAB-10926 | biostudies-arrayexpress

Effects of COVID-19 Pandemic on the Outcomes of Colorectal Cancer

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been identified as the cause of the Coronavirus disease 19 (COVID-19), which was initially reported in December 2019 in China and has since rapidly spread worldwide. Since then, the COVID-19 pandemic has caused a detrimental effect of the national health care system, causing a drastic reduction of the screening programs for colorectal cancer and requiring the redistribution of the hospital resources from elective surgery to the care of patients with SARS-Cov_2 infection requiring admission.

| 2364120 | ecrin-mdr-crc

Ad26.COV2.S Prevents SARS-CoV-2 Induced Pathways of Inflammation and Thrombosis in Hamsters

Project description:Syrian golden hamsters exhibit features of severe disease after SARS-CoV-2 challenge and are therefore useful models of COVID-19 pathogenesis and prevention with vaccines. Recent studies have shown that SARS-CoV-2 infection stimulates type I interferon, myeloid, and inflammatory signatures similar to human disease, and that weight loss can be prevented with vaccines. However, the impact of vaccination on transcriptional programs associated with COVID-19 pathogenesis and protective adaptive immune responses is unknown. Here we show that SARS-CoV-2 challenge in hamsters stimulates myeloid and inflammatory programs as well as signatures of complement and thrombosis associated with human COVID-19. Notably, single-dose immunization with Ad26.COV2.S, an adenovirus serotype 26 vector (Ad26)-based vaccine expressing a stabilized SARS-CoV-2 spike protein, prevents the upregulation of these pathways such that the gene expression profiles of vaccinated hamsters are comparable to uninfected animals. Furthermore, we validated the protective efficacy of the Ad26.COV2.S against proinflammatory pathways and coagulation cascade in rhesus macaques by proteomics. Finally, we show that Ad26.COV2.S vaccination induces T and B cell signatures that correlate with binding and neutralizing antibody responses. These data provide further insights into the mechanisms of Ad26.COV2.S based protection against severe COVID-19 in hamsters.

2022-03-26 | GSE196893 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data