[Rosiglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice].
OBJECTIVE
To study the effect of rosiglitazone on atherosclerosis and potential mechanism in ApoE-knockout mice.


METHODS
Thirty-two 6-week-old ApoE-knockout mice were used as atherosclerosis model in two groups: rosiglitazone group (n = 18) and control group (n = 14). Each group contained equal numbers of male and female mice. All mice were fed with normal chow diet. In addition to normal diet, rosiglitazone group received rosiglitazone 17 mg/kg of body weight/day. Venous bloods were collected for plasma glucose and lipid analysis, and aorta were prepared for morphologic and immunohistochemical analysis after 14 weeks. Aortic root (1 cm) was cut and prepared for paraffin slice. The histomorphometric analysis of atherosclerotic lesion was performed by means of HE; positive percentage of macrophage cell and tumor necrosis factor-alpha were measured by means of immunohistochemistry in cross section. The ratio of lesion/aortic wall surface in the rest aorta was measured by means of Sudan IV staining in longitudinal section.


RESULTS
The amount of fatty streak in rosiglitazone group was significantly greater than that of control group; the gross number of lesions and the number of fibrous plaque and atheromatous plaque were similar in two groups. There were no differences in percentage of lesions in cross section in two groups. Rosiglitazone could significantly reduce the extend of atherosclerosis of longitudinal section, decrease the amount of macrophage cell and the level of tumor necrosis factor-alpha in lesions. The plasma glucose was normal and similar in two groups, and total cholesterol, LDL-cholesterol and triglyceride were significantly higher in rosiglitazone group.


CONCLUSIONS
Rosiglitazone suppresses the expression of tumor necrosis factor-alpha, reduces the number of macrophage cell in lesion, and inhibits the development of atherosclerosis.
Zhao
Quan-ming
QM
Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Science, Beijing 100029, China. zhaoqm123@sohu.com
Yan
Dong
D
Song
Ai-li
AL
Wang
Wei
W
Shi
Qiang
Q
Wang
Lü-ya
LY
Chen
Dong
D
Fang
Wei
W
Wu
Ying
Y
Xu
Jin-peng
JP
Chen
Xin
X
Chen
Tie-jun
TJ
Mi
Shu-hua
SH
Lü
Shu-zheng
SZ
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001057:Apolipoproteins E; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone