[Prevention of rupture of atherosclerotic plaque by Candesartan in rabbit model].
OBJECTIVE
To evaluate Candesartan therapeutic effect against atherosclerotic plaque rupture and to explore the related mechanisms.


METHODS
Thirty-four New Zealand White male rabbits were randomly divided into three groups: the control group, the model control group and the Candesartan intervention group. The control group rabbits were fed with a normal diet. Rabbits of the latter two groups were fed with a 1% high-cholesterol diet and received a balloon catheter injury respectively one week after the cholesterol feeding. Candesartan (0.5 mgⁱkg⁻¹ⁱd⁻¹) was given to the Candesartan group rabbits 2 days before the performance of the balloon catheter injury. By the end of 12(th) week of the experiment, Russell's viper venom was used for rabbits of both the model control and the Candesartan groups in order to induce rupture of the plaques developed and followed by sacrifice of all the rabbits of the 3 groups. The aortas were removed and fixed for histological evaluation. Immunohistochemistry of MMP-9, macrophage markers and collagen were performed. The protein expression of MMP-9 was determined using Western blot analysis.


RESULTS
In the model control group, 7 of 9 rabbits with a total of 12 plaques developed rupture and thrombosis of the plaques after the induction. In contrast, only 2 of 10 rabbits with a total of 3 plaques demonstrated rupture and thrombosis in the Candesartan group (P < 0.05). The control group rabbits did not have plaque rupture and thrombosis. Compared with the model group, both the percentage area of MMP-9 and macrophages in the plaques were significantly decreased in the Candesartan group (12.35% ± 4.28% vs 32.58% ± 9.16%, P < 0.05; 13.87% ± 4.91% vs 23.8% ± 7.45%, P < 0.05). There was an increased percentage of collagen content in total plaques of the Candesartan group (30.27% ± 11.36% vs 4.18% ± 1.28%, P < 0.01). Compared with the model group, the protein expression of MMP-9 was significantly decreased in the Candesartan group (P < 0.01).


CONCLUSIONS
Candesartan has a preventive value against atherosclerotic plaque rupture in hypercholesterolemic rabbits, likely through its reduction of MMP-9 expression, inhibition of macrophage accumulation and increase of collagen content within the plaques.
Zhou
Xin-fu
XF
Department of Cardiology, Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. zxfskp@sina.com
Yin
Hong-chao
HC
Zhu
Wen-ling
WL
Shen
Li
L
Yu
Tao
T
Li
Shang-ai
SA
Meng
Zi-min
ZM
Wu
Ai-shan
AS
Qian
Huan-de
HD
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001012:Aorta, Abdominal / Q000293:injuries; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D003094:Collagen / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D011897:Random Allocation; D012422:Rupture, Spontaneous / Q000517:prevention & control; D013777:Tetrazoles / Q000627:therapeutic use*; D013927:Thrombosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D003094:Collagen; D020780:Matrix Metalloproteinase 9; C081643:candesartan