OBJECTIVE: To study the effects of pioglitazone on atherosclerosis on ApoE-/- mice, and to investigate the roles of adiponectin and its receptors. METHODS: ApoE-/- mice were fed with high-fat chow for the induction of atherosclerosis and were divided into three subgroups: placebo(n=10), low-dose[10 mg/( kg.d), n=10] pioglitazone therapy, and high-dose[20 mg/( kg.d), n=10] pioglitazone therapy. C57BL/6J wild type mice (n=9) were used as control. Aortic atherosclerosis and intimajmedia thickness (intima-media thickness , IMT) of abdominal aorta were monitored, and plasma adiponectin was also measured. Expression levels of the adiponectin receptor 1(AdipoR1)and adiponectin receptor 2 (AdipoR2) in vessels were analyzed(RT-PCR). RESULTS: (1) Aortic atherosclerotic lesions were observed in ApoE-/- mice but not in wild type mice. Interestingly, these lesions were significantly prevented by high-dose pioglitazone therapy. Compared with wild type mice, ApoE-/- mice had increased IMT of abdominal aorta [(0.290+/-0.063 vs 0.178+/-0.012) cm, P<0.01] that was significantly reversed by high-dose pioglitazone therapy [(0.208+/-0.012 vs 0.290+/-0.063) cm, P<0.05]. (2) The level of plasma adiponectin was significantly lower in ApoE-/- mice [(12.41+/-3.84 vs 18.96+/-4.89) microg/L, P<0.05), which could be increased by low-and high-dose pioglitazone therapy (18.78+/-7.24 microg/L vs 12.41+/-3.84 microg/L, P<0.05; and 24.00+/-4.71 microg/L vs 12.41+/-3.84 microg/L, P<0.05). (3) Compared with wild type mice, ApoE-/- mice had reduced AdipoR1 mRNA level(0.789+/-0.167 vs 0.950+/-0.071, P<0.05) and reduced the ratio of AdipoR1/AdipoR2 (0.940+/-0.102 vs 1.039+/-0.062, P<0.05); high dose pioglitazone therapy could upregulate AdipoR1, AdipoR2 mRNA expression and increase the ratio of AdipoR1/AdipoR2 (1.063+/-0.051 vs 0.940+/-0.102,P<0.01). CONCLUSION: Pioglitazone inhibits aortic atherosclerosis in ApoE-/- mice, and these effects are correlated with increased plasma adiponectin level and the expression of AdipoR1 mRNA in vessels.
OBJECTIVE: To study the effects of pioglitazone on atherosclerosis on ApoE-/- mice, and to investigate the roles of adiponectin and its receptors. METHODS:ApoE-/- mice were fed with high-fat chow for the induction of atherosclerosis and were divided into three subgroups: placebo(n=10), low-dose[10 mg/( kg.d), n=10] pioglitazone therapy, and high-dose[20 mg/( kg.d), n=10] pioglitazone therapy. C57BL/6J wild type mice (n=9) were used as control. Aortic atherosclerosis and intimajmedia thickness (intima-media thickness , IMT) of abdominal aorta were monitored, and plasma adiponectin was also measured. Expression levels of the adiponectin receptor 1(AdipoR1)and adiponectin receptor 2 (AdipoR2) in vessels were analyzed(RT-PCR). RESULTS: (1) Aortic atherosclerotic lesions were observed in ApoE-/- mice but not in wild type mice. Interestingly, these lesions were significantly prevented by high-dose pioglitazone therapy. Compared with wild type mice, ApoE-/- mice had increased IMT of abdominal aorta [(0.290+/-0.063 vs 0.178+/-0.012) cm, P<0.01] that was significantly reversed by high-dose pioglitazone therapy [(0.208+/-0.012 vs 0.290+/-0.063) cm, P<0.05]. (2) The level of plasma adiponectin was significantly lower in ApoE-/- mice [(12.41+/-3.84 vs 18.96+/-4.89) microg/L, P<0.05), which could be increased by low-and high-dose pioglitazone therapy (18.78+/-7.24 microg/L vs 12.41+/-3.84 microg/L, P<0.05; and 24.00+/-4.71 microg/L vs 12.41+/-3.84 microg/L, P<0.05). (3) Compared with wild type mice, ApoE-/- mice had reduced AdipoR1 mRNA level(0.789+/-0.167 vs 0.950+/-0.071, P<0.05) and reduced the ratio of AdipoR1/AdipoR2 (0.940+/-0.102 vs 1.039+/-0.062, P<0.05); high dose pioglitazone therapy could upregulate AdipoR1, AdipoR2 mRNA expression and increase the ratio of AdipoR1/AdipoR2 (1.063+/-0.051 vs 0.940+/-0.102,P<0.01). CONCLUSION:Pioglitazone inhibits aortic atherosclerosis in ApoE-/- mice, and these effects are correlated with increased plasma adiponectin level and the expression of AdipoR1 mRNA in vessels.