[Role of adiponectin and its receptors in anti-atherosclerotic effects of pioglitazone on ApoE knocked out mice].
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).


CONCLUSIONS
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.
Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
Ci-ren
CR
Da-Wa
Feng
F
Zhao
Yong-fen
YF
Qi
Lu-zeng
LZ
Chen
Yong
Y
Huo
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
D052242:Adiponectin; D001057:Apolipoproteins E; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D045162:Thiazolidinediones; D000077205:Pioglitazone