PSGL-1 Deficiency is Protective Against Inflammation-induced Endothelial...

Heart disease is the leading cause of death in the US, and is often caused by inflammatory conditions, including obesity.  Inflammation in the body involves the recruitment of leukocytes by adhesion molecules, and it has been found that P-selectin glycoprotein ligand-1 (Psgl-1) is an important leukocyte ligand for the adhesion molecules P-selectin and E-selectin.  Endothelial function of vessels is impaired during inflammation and in turn promotes the upregulation of adhesion molecules.  Psgl-1 deficiency inhibits leukocyte-endothelial interactions, and therefore we hypothesized it may be protective against the endothelial dysfunction caused by inflammation.  By studying the vascular contraction and relaxation of mesenteric arteries from Psgl-1 deficient mice, it was found that Psgl-1 deficiency repairs the endothelial function in both diet-induced obese mice and mice injected with the endotoxin lipopolysaccharide.  These findings provide valuable insight into the mechanism of inflammation-induced endothelial dysfunction.