Author(s): DaWa CR, Zhao F, Qi YF, Chen LZ, Huo Y
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Abstract 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.
This article was published in Beijing Da Xue Xue Bao
and referenced in Journal of Diabetes & Metabolism