This study identifies Copine 5 (CPNE5) as a critical factor in the development of life-threatening sepsis-induced vascular leakage and mortality. Analysis of human aorta cells revealed that CPNE5 is the primary Copine family member expressed in endothelial cells, which form the lining of blood vessels.

In both human sepsis patients and a mouse model of sepsis, plasma levels of CPNE5 were found to be significantly reduced, inversely correlating with elevated markers of vascular injury like Ang-II, sICAM-1, and SDC-1.

Further experiments using cultured endothelial cells (ECs) showed that inflammatory stimuli (LPS or Cytomix) reduce CPNE5 levels, which in turn leads to increased endothelial permeability (leakage).

Critically, knocking down CPNE5 in ECs or deleting the $CPNE5$ gene in mice resulted in hyperpermeability, organ damage, and increased mortality following septic challenge.

These consistent findings across human patients, mice, and cell models suggest that the drop in plasma CPNE5 levels is not just a marker but a potential contributor to the dangerous vascular leakage associated with sepsis, highlighting CPNE5 as a promising therapeutic target.

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