Premium
Oral rapamycin attenuates inflammation and enhances stability of atherosclerotic plaques in rabbits independent of serum lipid levels
Author(s) -
Chen Wen Qiang,
Zhong Lin,
Zhang Lei,
Ji Xiao Ping,
Zhang Mei,
Zhao Yu Xia,
Zhang Cheng,
Zhang Yun
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2008.00102.x
Subject(s) - medicine , simvastatin , inflammation , vulnerable plaque , pathology , gastroenterology
Background and purpose: Atherosclerotic plaque rupture and thrombosis are the main cause of acute coronary syndrome. The study was aimed to test the hypothesis that oral administration of rapamycin may attenuate inflammation, inhibit progression and enhance stability of atherosclerotic plaques. Experimental approach: Thirty New Zealand rabbits were subjected to balloon‐induced endothelial injury of the abdominal aorta and were fed a diet of 1% cholesterol for 20 weeks. From week 9 to week 20, the animals were treated with oral rapamycin (0.5 mg·kg −1 ·day −1 ; group A), oral simvastatin (5 mg·kg −1 ·day −1 ; group B) and no drugs (group C). At the end of week 20, all rabbits were challenged with injection of Chinese Russell's viper venom and histamine. Serological, ultrasonographic, pathological, immunohistochemical and gene expression studies were performed. Key results: Rapamycin significantly increased the thickness of the fibrous caps and decreased plaque vulnerability index in group A rabbits. Serum lipid levels were higher whereas plaque burden was lower in group A than in group B ( P < 0.05). The incidence of plaque rupture in group A (0%) and group B (0%) was significantly lower than that in group C (56.0%, P < 0.05). Conclusions and implications: Oral administration of rapamycin effectively attenuated inflammation, inhibited progression and enhanced stability of atherosclerotic plaques in rabbits, without altering serum lipid levels. Our findings suggest a novel approach to the treatment of atherosclerosis.