AIM:To investigate the role of proviral integration site for Moloney murine leukemia virus 1(PIM1)in the phenotypic switching of vascular smooth muscle cells(VSMCs)induced by oxidized low-density lipoprotein(oxLDL),and to explore the underlying mechanisms.METHODS:Eighteen male ApoE-/-mice(8 weeks old)were ran-domly divided into general diet group and high-fat diet group,with 9 mice per group.After 16 weeks,aortic samples were analyzed using HE staining to observe plaque formation.In vitro,VSMCs were exposed to oxLDL to induce phenotypic transformation.Western blot and immunofluorescence were used to measure the protein expression levels of PIM1 and phe-notypic markers including α-smooth muscle actin(α-SMA),smooth muscle protein 22α(SM22α),osteopontin(OPN),and CD68.Glycolysis levels were assessed by detecting the expression of glycolytic enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase(PFKFB3)and hexokinase 2(HK2)by Western blot,and lactate secretion was measured using a lactate test kit.The effects of SMI-4a(a specific inhibitor of PIM1)and PIM1 small interfering RNA on oxLDL-in-duced phenotypic markers in VSMCs were evaluated.Moreover,the impact of 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one(3PO;a glycolysis inhibitor)on oxLDL-induced phenotypic switching and glycolysis in VSMCs was investigated.RESULTS:HE staining revealed atherosclerotic plaque formation in the aortas of ApoE-/-mice fed with high-fat diet.Im-munofluorescence showed high accumulation of PIM1 and OPN in the tunica intima of atherosclerotic plaques.Compared with control group,aortic plaques exhibited significantly elevated levels of PIM1,OPN and CD68 proteins(P<0.01),ac-companied by reduced expression of contractile phenotype markers α-SMA and SM22α(P<0.01).In vitro,oxLDL treat-ment led to gradual decrease in α-SMA and SM22α expression(P<0.05 or P<0.01),while OPN and CD68 expression in-creased(P<0.05 or P<0.01).Moreover,oxLDL significantly up-regulated the protein expression of PIM1,PFKFB3 and HK2,and increased lactate secretion in VSMCs(P<0.05 or P<0.01).Knockdown of PIM1 or treatment with SMI-4a markedly attenuated these oxLDL-induced effects on VSMCs(P<0.05 or P<0.01).Treatment with 3PO also abolished ox-LDL-induced phenotypic transformation and glycolysis in VSMCs(P<0.05 or P<0.01).CONCLUSION:PIM1 highly accumulates in the atherosclerotic plaques of ApoE-/-mice.The phenotypic transformation of VSMCs was correlated with the expression of PIM1.PIM1 can regulate the phenotypic transformation of oxLDL-treated VSMCs by inducing glycolysis.