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The following is a summary of “Bortezomib induces Rho-dependent hyperpermeability of endothelial cells synergistically with inflammatory mediators,” published in the December 2024 issue of Pulmonology by Nishima et al.
Bortezomib (BTZ), a selective 26 S proteasome inhibitor, was clinically used for treating multiple myeloma and mantle cell lymphoma, but pulmonary complications, including capillary leak syndrome, were reported prior to its approval, with the underlying mechanism remaining unclear.
Researchers conducted a retrospective study to investigate the influence of BTZ on endothelial cell permeability.
They explored the impact of BTZ on vascular endothelial cells, specifically focusing on RhoA and RhoC protein activity. Stress fiber formation, an established indicator of increased permeability, was evaluated through the Rho/ROCK pathway.
The results showed BTZ increased the protein levels of RhoA and RhoC in vascular endothelial cells, promoting stress fiber formation via the Rho/ROCK pathway. This led to a Rho-dependent increase in vascular permeability. Additionally, the stress fiber formation induced by BTZ exhibited synergistic effects with histamine, an inflammatory mediator.
Investigators concluded the BTZ increased RhoA and RhoC protein levels in endothelial cells, amplifying vascular permeability during pulmonary inflammation and enhancing inflammatory responses.
Source: bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-024-03387-x
