Simvastatin Preserves Human Microvascular Endothelial Barrier Function Through Mevalonate-Dependent Regulation of RhoB Localization and Activation

Simvastatin pretreatment preserves TNF-stimulated barrier function in human dermal microvascular endothelial cells, maintaining transendothelial electrical resistance and ZO-1/claudin-5 organization.

• Why it matters: Endothelial barrier failure drives edema and organ dysfunction in inflammatory critical illness, but it is unclear whether clinically used statins can modulate RhoB-linked barrier disruption.
• What they did: Human dermal microvascular endothelial cells were pretreated with simvastatin before TNF exposure; barrier readouts included transendothelial electrical resistance, junctional ZO-1/claudin-5, and RhoB localization/activation with mevalonate rescue.
• The result: Simvastatin shifted RhoB from membrane to nucleus, reduced active RhoB and myosin light chain phosphorylation; RhoB silencing matched its protection, and mevalonate reversed both barrier preservation and RhoB/MLC changes.

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