Key result
VEGF inhibition is linked to enriched oxidative, inflammatory, and NF-κB pathways plus vascular stress.
Why the study?
Vascular endothelial growth factor inhibitors are frequently associated with cardiovascular toxicities such as hypertension and endothelial dysfunction, but the molecular mechanisms underlying these adverse effects remain incompletely understood.
Does VEGF inhibition induce oxidative and inflammatory vascular stress responses in pre-treatment cancer cohort tumours and human vascular cells?
Does VEGF inhibition induce oxidative and inflammatory vascular stress responses in pre-treatment cancer cohort tumours and human vascular cells?
Answers are grounded in this paper and cite their sources.
VEGF inhibition is associated with a coordinated redox-inflammatory response and extracellular vesicle release in vascular cells, offering a potential molecular mechanism for VEGFi-induced vascular dysfunction and cardiovascular toxicity.
Vascular endothelial growth factor inhibitors (VEGFi) are widely used in the treatment of advanced malignancies, including clear cell renal cell carcinoma (ccRCC), but are frequently associated with cardiovascular toxicities such as hypertension and endothelial dysfunction. The molecular mechanisms underlying these adverse effects remain incompletely understood. In this study, we performed an integrated transcriptomic and functional analysis to characterise vascular stress responses associated with VEGFi. Pre-treatment tumour RNA sequencing data from a public cancer cohort were analysed using Gene Set Enrichment Analysis (GSEA) to identify pathway-level signatures associated with subsequent VEGFi treatment. No individual genes remained significant after multiple testing correction; therefore, emphasis was placed on coordinated biological responses. Functional validation was conducted in human vascular cells treated with a VEGFi to assess reactive oxygen species (ROS) production, cytokine levels and expression, and extracellular vesicles (EVs) release. Pathway analysis revealed significant baseline enrichment of oxidative stress, inflammatory response, and nuclear factor-kappa B (NF-κB) signalling pathways in tumours of patients who subsequently received VEGFi. These baseline associations were complemented by increased vascular cell ROS production and enhanced EVs release in vitro. Inflammatory activation was further confirmed by increased cytokine secretion, despite unchanged messenger RNA expression, indicating regulation at post-transcriptional and secretory levels. Collectively, these baseline tumour signatures and the in vitro vascular findings are consistent with a model in which VEGF inhibition induces a coordinated redox-inflammatory response, which may involve EV-mediated intercellular communication. This mechanism may contribute to vascular dysfunction and cardiovascular toxicity associated with VEGFi-targeted therapies.
No takes yet. Share an insight, caveat, or question.
SILVA et al. (2026) studied Advanced malignancies (including clear cell renal cell carcinoma) and cardiovascular toxicity. Vascular endothelial growth factor inhibitors (VEGFi) was evaluated on Pathway-level transcriptomic signatures and in vitro vascular stress responses (ROS production, cytokine levels, and extracellular vesicle release). VEGF inhibition was associated with baseline tumour enrichment of oxidative stress, inflammatory, and NF-κB pathways, plus increased in vitro vascular ROS, cytokine, and EV release.
Synapse has enriched 10 related papers. Consider them for comparative context: