Vascular endothelial growth factor A: friend or foe in the pathogenesis of HIV and SARS-CoV-2 infections?

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 14

Published: Feb. 11, 2025

This review article discusses the role of vascular endothelial growth factor A (VEGF-A) in pathogenesis SARS-CoV-2 and HIV infection, both conditions being renowned for their impact on endothelium. The processes involved homeostasis angiogenesis are reviewed briefly before exploring interplay between hypoxia, VEGF-A, neuropilin-1 (NRP-1), inflammatory pathways. We then focus infection show how binding viral pathogen to angiotensin-converting enzyme 2 receptor, as well NRP-1, leads elevated levels VEGF-A consequences such coagulation, dysfunction, inflammation. augments via several mechanisms, most prominently, by trans-activator transcription ( tat ) protein mimicking its VEGFR-2, upregulation which enhances interaction VEGFR-2. propose that observed during HIV/SARS-CoV-2 co-infection originate predominantly from activated immune cells due HIF-1α damaged cells. In this context, a few clinical trials have described diminished requirement oxygen therapy anti-VEGF treatment infection. currently available strategies target VEGFR-1 blocking receptors could, however, lead negative outcome, inhibiting not only pathological, but also physiological angiogenesis. Based examination published studies, suggests targeting selective inhibition may be beneficial context

Language: Английский

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VEGF-A in COVID-19: a systematic review and meta-analytical approach to its prognostic value

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 12, 2025

Abstract Numerous studies have reported vascular endothelial growth factor A (VEGF-A) has a significant impact on the pathophysiology of COVID-19. The objective this systematic review and meta-analysis is to determine prognostic value increased levels VEGF-A in individuals with literature search was conducted across multiple electronic databases, including PubMed, Web Science, Cochrane Library, Scopus, EMBASE, Google Scholar, up January 2024. Studies examining serum or plasma COVID-19 patients were incorporated, specific attention given contrasting severe/critical cases against moderate cases. Standardized mean differences (SMD) 95% confidence intervals (CIs) calculated using random-effects model overall effect sizes. Meta-regressions subgroup analyses performed explore potential sources heterogeneity. synthesized data from 11 involving total 1119 patients. Elevated significantly associated disease severity, pooled SMD 0.525 (95% CI 0.239–0.058; P = 0.028). Research indicated that nature relationship differs among various age groups, there minor discrepancies techniques employed obtain measurements. Furthermore, meta-regression analysis correlation between assay technique body mass index (BMI). This provides compelling evidence for potency Understanding intricate interplay holds promise development targeted therapeutic strategies indicators management

Language: Английский

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Sema3A relieves Neuropathic Pain by Reducing eIF2α Phosphorylation via Suppressing PI3K/Akt/mTOR Pathway

Journal of Pain, Journal Year: 2025, Volume and Issue: unknown, P. 105374 - 105374

Published: March 1, 2025

Language: Английский

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Hypoxia signaling in cancer: HIF-1α stimulated by COVID-19 can lead to cancer progression and chemo-resistance in oral squamous cell carcinoma (OSCC)

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 26, 2025

Language: Английский

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Possible involvement of neuropeptide Y sub-receptor 1 (NPY-Y1) in the anti-viral response of SARS-CoV-2 infection in Syrian hamster

Biomedical Research, Journal Year: 2025, Volume and Issue: 46(2), P. 37 - 50

Published: April 4, 2025

Co-administration of Molnupiravir and Remdesivir, treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), inhibits viral replication infectivity. Previous studies indicate that the neuropeptide Y sub-receptor 1 (NPY-Y1) is involved in influenza virus aggravation mouse pulmonary phagocytes, but exact mechanisms remain unclear. Understanding NPY-Y1 receptor's involvement SARS-CoV-2 both mice hamsters may help explore its potential as an indicator infections support development preventive care. This study examined effects Remdesivir on infected Syrian NPY pathway during infection. infection increased mRNA expression NPY, receptors, inflammatory cytokines chemokines hamster lungs. drugs significantly reduced these expressions. Changes receptor were correlated with IL-10, IL-12, IFN-γ, implying a role antiviral response pathway. These findings highlight changes levels are influenced by impact NPY-NPY-Y1 cascade. implies pathway's responses therapeutic target.

Language: Английский

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The levels of inflammatory, angiogenic, and stress biomarkers in plasma of donors depending on anti-SARS-CoV-2 IgG titers

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Journal Year: 2025, Volume and Issue: 21(2), P. 112 - 120

Published: April 1, 2025

Background. Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has led to widespread illness and global health challenges. While phase of infection been extensively studied, long-term effects, particularly in individuals who have recovered, remain unclear. Post-acute complications SARS-CoV-2 involves prolonged symptoms systemic disorders, including persistent inflammation, endothelial dysfunction, immune dysregulation, which often last for months. Among key factors contributing these conditions, there are pro-inflammatory cytokines, growth involved angiogenesis, hypoxia-inducible stress-related proteins, play a significant role tissue repair response modulation. The research aimed evaluate degree determine levels pro-angiogenic factors, сellular hypoxia marker HIF-1α, heat shock such as HSP60 HSP70, plasma healthy donors recovered from COVID-19, with particular focus on relationship between biomarkers anti-SARS-CoV-2 IgG titers. Materials methods. This ages 25 45 years, had COVID-19 at least 3 6 months prior beginning study. All patients were divided into groups based their inflammatory TNF-α, transcription factor NF-κB, angiogenic VEGF, PDGF FGF-2, hypoxic proteins measured enzyme-linked immunosorbent assay. Group differences analyzed using ANOVA Tukey’s test or Kruskal-Wallis Dunn’s test, presenting results median interquartile range, significance p ≤ 0.05. Results. study found parameters among donor varying There was an increase markers, TNF-α higher PDGF, FGF-2 showed distinct patterns, VEGF generally reduced, except group titers 95 ± 5 125 10 Index (S/C), where they significantly increased. notably 175 (S/C). HIF-1α also increased 75 (S/C) compared those without IgG. In contrast, HSP70 reduced all reference group, could indicate possible abnormalities mechanisms stress after COVID-19. Conclusions. Our suggest that activation, angiogenesis-related pathways crucial pathogenesis post-COVID-19 complications, underscoring need therapeutic strategies address chronic impaired recovery.

Language: Английский

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Epigenetic patterns, accelerated biological aging, and enhanced epigenetic drift detected 6 months following COVID-19 infection: insights from a genome-wide DNA methylation study

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Aug. 20, 2024

The epigenetic status of patients 6-month post-COVID-19 infection remains largely unexplored. existence long-COVID, or post-acute sequelae SARS-CoV-2 (PASC), suggests potential long-term changes. Long-COVID includes symptoms like fatigue, neurological issues, and organ-related problems, regardless initial severity. mechanisms behind long-COVID are unclear, but virus-induced changes could play a role. Our study explores the lasting impacts infection. We analyzed genome-wide DNA methylation patterns in an Italian cohort 96 6 months after COVID-19 exposure, comparing them to 191 healthy controls. identified 42 CpG sites with significant differences (FDR < 0.05), primarily within islands gene promoters. Dysregulated genes highlighted links glutamate/glutamine metabolism, which may be relevant PASC symptoms. Key significance effects include GLUD1, ATP1A3, ARRB2. Furthermore, Horvath's clock showed slight age acceleration patients. also observed substantial increase stochastic mutations (SEMs) group, implying drift. SEM analysis 790 affected genes, indicating dysregulation pathways related insulin resistance, VEGF signaling, apoptosis, hypoxia response, T-cell activation, endothelin signaling. provides valuable insights into consequences COVID-19. Results suggest possible associations accelerated aging, drift, disruption critical biological linked immune vascular health. Understanding these crucial for elucidating complex developing targeted therapeutic interventions.

Language: Английский

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Effects of SARS-COV-2 on molecules involved in vascularization and autophagy in placenta tissues

Journal of Molecular Histology, Journal Year: 2024, Volume and Issue: 55(5), P. 753 - 764

Published: Aug. 1, 2024

SARS-CoV-2 infection is considered as a multi-organ disease, and several studies highlighted the relevance of virus in induction vascular injury tissue morphological alterations, including placenta. In this study, immunohistochemical analyses were carried out on placenta samples derived from women with COVID-19 at delivery (SARS-CoV-2 PCR+) or healed negative delivery, PCR-) who gave birth before 2019 (Control). Angiotensin Converting Enzyme 2 (ACE2) receptor, Cluster differentiation 147 (CD147), endothelial CD34 marker, Vascular Endothelial Growth Factor (VEGF) total Microtubule-associated protein 1 Light Chain 3B marker (LC3B) investigated parallel SPIKE by standard IHC. Multiplexed Immunohistochemical Consecutive Staining Single Slide (MICSSS) was used to examine antigen co-expression same specimen. detected villi decidua ongoing infection, no significant differences staining between both biopsy sites. VEGF significantly increased PCR + biopsies compared control PCR- samples, MICSSS method showed co-localization CD34. The autophagy, suggested LC3B increase protein, may explain one different mechanisms which react infection. These data could provide important information impact that have mother-to-fetus transmission.

Language: Английский

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VEGFR1 TK signaling protects the lungs against LPS-induced injury by suppressing the activity of alveolar macrophages and enhancing the anti-inflammatory function of monocyte-derived macrophages

Toxicology and Applied Pharmacology, Journal Year: 2024, Volume and Issue: 492, P. 117083 - 117083

Published: Sept. 2, 2024

Acute lung injury (ALI) is characterized by hyperinflammation followed vascular leakage and respiratory failure. Vascular endothelial growth factor (VEGF)-A critical for capillary permeability; however, the role of VEGF receptor 1 (VEGFR1) signaling in ALI progression remains unclear. Here, we show that deletion VEGFR1 tyrosine kinase (TK) mice exacerbates lipopolysaccharide (LPS)-induced as evidenced excessive pro-inflammatory cytokine production interleukin(IL)-1β-producing neutrophil recruitment to inflamed tissues. development involves reduced alveolar macrophage (AM) levels monocyte-derived macrophages (MDMs) a TK-dependent manner. TK cultured AMs. TK-expressing MDMs displayed an anti-inflammatory phenotype. Additionally, transplantation bone marrow (BM)-derived into TK-deficient inflammation. Treatment with placental (PlGF), agonist VEGFR1, protected against LPS-induced associated increased MDMs. These results suggest prevents suppressing activity AMs enhancing function

Language: Английский

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Human adenovirus type 7 (HAdV-7) infection induces pulmonary vascular endothelial injury through the activation of endothelial autophagy

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 4, 2024

HAdV-7 is a prevalent pathogen that can cause severe pneumonia in children. Previous studies have shown significant increase serum levels of vascular permeability factor (VPF/VEGF) and viral load pediatric patients with fatal infection, suggesting potential damage to the pulmonary endothelium. Further research necessary elucidate underlying mechanism. The human lung microvascular endothelial cell line-5a CD46 mice were used for vitro vivo experiments, respectively. RNA-seq was employed correlative omics analysis. Viral infection copy status examined using transmission electron microscopy observe virus particles, immunofluorescence detect protein Hexon, qPCR assess fiber gene copies. Various methods, including ELISAs VEGF other injury markers, CCK8 assay viability, flow cytometry endothelium numbers, evaluate damage. Acute severity evaluated by scoring pathological inflammation measuring permeability. Autophagy activation assessed observing autophagosomes validating marker proteins. GSEA analysis showed enrichment sets related functions (barrier, defense, regeneration) ALI HAdV-7-infected group. GO indicated an autophagy-related pathways linked death. Subsequently, successful signs replication observed endothelium, cytopathic effects, intracellular virions, increased Endothelial injury, mitochondrial damage, decreased elevated markers such as VEGF, sICAM-1, sVCAM-1, E-selectin, ESM1, MCP1, IL1β after infection. Additionally, evidence leaky blood vessels observed, progressive weight loss, permeability, consolidation. Furthermore, induced autophagosome formation triggered complete autophagy. Importantly, inhibiting autophagic flux reduced load, improved survival rate, alleviated vessel leakage, mitigated inflammation. successfully infects replicates effectively, causing high expression serum, well ALI/ARDS. inhibitors alleviate inhibit replication, relieve leakage from vasculature, reduce

Language: Английский

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