Abstract: Objective To investigate the effects of Src Homology 2 Containing Protein Tyrosine Phosphatase 2(SHP2)specific inhibitor phenylhydrazonopyrazolonesulfonate1(PHPS1) on the progression of AS in apoE-/- mice.
Methods Early AS model was constructed in 28 apoE-/- mice on 1.25% high-cholesterol feed for 4 weeks, and they were randomly divided into control group and PHPS1 group. The size and cell components of descending aorta plaques were observed to evaluate the changes in the contents of the signaling pathway, scavenger receptor(SR) protein and mRNA in the plaques. Oxidized low density lipoprotein(ox-LDL) and green fluorescent microspheres with or without PHPS1 intervened bone marrow-derived macrophage(BMDM)cells in 16 h, and observed green fluorescent deposition of the BMDM.
Results The area of oil red O, the size of plaques and the content of macrophages in plaques in PHPS1 group were significantly increased compared with the control group, and the differences were statistically significant(P＜0.01). The green fluorescence intensity of macrophages in PHPS1 group was significantly higher than that in the control group(P＜0.01). The mRNA expression levels of cluster of differentiation 36(CD36) and scavenger receptorA1(SRA1) in PHPS1 group were significantly higher than those in the control group, and the differences were statistically significant(P＜0.01). Phosphorylated extracellular regulated kinases(p-ERK), phosphorylated phosphatidylinositol 3-kinase(p-PI3K) and phosphorylated protein kinase B(p-AKT) in the PHPS1 group were significantly higher than those in the control group.The differences were statistically significant(P＜0.01).
Conclusion PHPS1 mainly affects the overexpression of SR through extracellular-regulated kinases and phosphatidylinositol 3-kinase/protein kinase B signaling pathways, thereby increasing the phagocytosis of ox-LDL by macrophages and ultimately promoting the formation of foam cells and the progression of AS.

Key words: atherosclerosis, tyrosine phosphatase SHP-2, PHPS1