Microvascular leak plays a critical role in the outcome of sepsis. Counteracting vascular leakage has recently raised a huge interest in the field but therapeutic targets and translation studies are crucially lacking. The inventors hypothesized that ANGPTL4 might counteract lipopolysaccharide-induced vascular hyperpermeability. Mechanistically, the inventors show that the C-terminal fragment of ANGPTL4 recapitulates full-length ANGPTL4 inhibition of vascular permeability by stabilizing endothelial cell adherent junctions whereas the N-terminus has no such effect. The inventors further demonstrate that giving human recombinant c-ANGPTL4 to mice prevents microvascular leak and mortality induced by LPS. In humans, the inventors describe the association between ANGPTL4 plasma level at time of inclusion and 90-day mortality in sepsis or septic shock patients French and European Outcome Registry in Intensive Care Units (FROG-ICU). In conclusion, the inventors demonstrate that suppressing vascular permeability by c-ANGPTL4 could be a novel therapeutic for the treatment of sepsis capillary leak syndrome. Either alone or in combination with existing drugs, c-ANGPTL4 could contribute to the reduction of mortality in patients with shock states.