[Study of carvedilol on plaque stability in carotid atherosclerotic rabbits transfected by p53 gene].
OBJECTIVE
To investigate the effects of carvedilol on stabilizing atherosclerosis plaque.


METHODS
Forty five male Japanese white rabbits were divided randomly into 5 groups with 9 for each. One group was fed up with normal diet as blank control. In other four groups, the common carotid artery of rabbits fed up with high cholesterol diet were injured by balloon. Three groups of them were transfected by wild-type p53 gene 8 weeks later, and then two groups of them were treated with carvedilol (3 mgxkg(-1)xd(-1)) and metoprolol (6 mgxkg(-1)xd(-1)) respectively, high cholesterol diet should be continued for other 4 weeks. Serum lipid, hypersensitive C-reaction protein (hsCRP), oxidized low density lipoprotein (oxLDL), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were measured in 0, 8, 12 weeks after experiment. The apoptosis rate of smooth muscle cell (SMC) in endomembrane and the local expression of p53, bcl-2, bax, alpha-actin were examined after experiment, and the carotid arteries were examined by light microscopy and transmission electron microscopy.


RESULTS
The typical carotid atherosclerotic plaques were observed in balloon-injured groups. The local expression rates of p53 in groups transfected by wild type p53 gene were higher obviously than them in other two groups (P < 0.01). Compared with the rabbits received simple transfection, the thickness of the fibrous cap in rabbits received carvedilol and metoprolol were all increased, but the change could be observed significantly in carvedilol group (P < 0.05). Compared with metoprolol, carvedilol could reduce the level of serum hsCRP, oxLDL, MDA, and increase the concentration of SOD and GSH-PX significantly (P < 0.05 or 0.01), but two medicines had no obvious influence to serum lipid. The apoptosis rate of SMC in endomembrane, the local expression of bax gene and bax/bcl-2 ratio were decreased, the positive expression rates of alpha-actin and bcl-2 were enhanced in carvedilol group (P < 0.01).


CONCLUSIONS
Both carvedilol and metoprolol can improve the stability of the plaque, but carvedilol is superior. Its mechanisms may lie in that carvedilol still has function of anti-inflammation, anti-oxidation, decreasing the apoptosis rate of SMC in addition to its function of blocking beta-receptor.
Guan
Yun-yuan
YY
Department of Cardiology, Second Affiliated Hospital of Nantong University, Nantong 226001, China. 32514@vip.sina.com
Ye
Bing-hua
BH
Lu
Hui-he
HH
Sheng
Zhen-qiang
ZQ
Zhang
Li
L
Hua
Shou-ming
SM
Tao
Guo-hua
GH
Yang
Qi-chang
QC
D000821:Animal Feed; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology*; D002340:Carotid Artery Diseases / Q000235:genetics / Q000473:pathology*; D000077261:Carvedilol; D016158:Genes, p53; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D002227:Carbazoles; D011412:Propanolamines; D016159:Tumor Suppressor Protein p53; D000077261:Carvedilol; D008790:Metoprolol