Lipopolysaccharide induces a fibrotic‐like phenotype in endothelial cells

Endothelial dysfunction is crucial in endotoxaemia‐derived sepsis syndrome pathogenesis. It is well accepted that lipopolysaccharide ( LPS ) induces endothelial dysfunction through immune system activation. However, LPS can also directly generate actions in endothelial cells ( EC s) in the absence of participation by immune cells. Although interactions between LPS and EC s evoke endothelial death, a significant portion of EC s are resistant to LPS challenge. However, the mechanism that confers endothelial resistance to LPS is not known. LPS ‐resistant EC s exhibit a fibroblast‐like morphology, suggesting that these EC s enter a fibrotic programme in response to LPS . Thus, our aim was to investigate whether LPS is able to induce endothelial fibrosis in the absence of immune cells and explore the underlying mechanism. Using primary cultures of EC s and culturing intact blood vessels, we demonstrated that LPS is a crucial factor to induce endothelial fibrosis. We demonstrated that LPS was able and sufficient to promote endothelial fibrosis, in the absence of immune cells through an activin receptor–like kinase 5 ( ALK 5) activity–dependent mechanism. LPS ‐challenged EC s showed an up‐regulation of both fibroblast‐specific protein expression and extracellular matrix proteins secretion, as well as a down‐regulation of endothelial markers. These results demonstrate that LPS is a crucial factor in inducing endothelial fibrosis in the absence of immune cells through an ALK 5‐dependent mechanism. It is noteworthy that LPS ‐induced endothelial fibrosis perpetuates endothelial dysfunction as a maladaptive process rather than a survival mechanism for protection against LPS . These findings are useful in improving current treatment against endotoxaemia‐derived sepsis syndrome and other inflammatory diseases.