The metabonomics study of P-selectin glycoprotein ligand-1 (PSGL-1) deficiency inhibiting the progression of atherosclerosis in LDLR(-/-) mice

Atherosclerosis (AS) is a multi-factorial chronic disease commonly associated with the mechanisms of metabolism disorder, endothelial dysfunction and chronic inflammation. AS an inflammatory molecule, p-selectin glycoprotein ligand-1 (PSGL-1) played an important role in the inflammatory process of atherogenesis involving the recruitment of leukocyte and transmitting signals to activate leukocyte during the adhesion process. So far, there has been little study regarding the effects of PSGL-1 on AS progression and the metabolic regulation. In this report, we studied the effect of PSGL-1 deficiency on the formation and progression of AS and the metabolic regulation by use of LDLR(-/-), PSGL-1(-/-) transgenic mice based on metabonomics. It was found that the PSGL-1 deficiency reduced the atherosclerotic plaque area, inflammatory cells infiltration and fiber hyperplasia during the AS development. The serum metabonomics study showed that the LDLR(-/-) ,PSGL-1(-/-) mice had higher levels of HDL, valine, acetate, pyruvate, choline, PC, GPC and glycine, and lower levels of LDL+VLDL and lactate at the early stage of atherosclerosis, while lactate, citrate and glutamine showed statistical significance at the late stage of atherosclerosis. These results showed that the PSGL-1 deficiency inhibited the AS progression and regulated glucose metabolism, lipid metabolism, amino acid and phospholipid metabolism in LDLR(-/-) mice.