Oral rapamycin attenuates inflammation and enhances stability of atherosclerotic plaques in rabbits independent of serum lipid levels.
OBJECTIVE
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.


METHODS
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 x kg(-1) x day(-1); group A), oral simvastatin (5 mg x kg(-1) x 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.


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
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.
Chen
Wen Qiang
WQ
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.
Zhong
Lin
L
Zhang
Lei
L
Ji
Xiao Ping
XP
Zhang
Mei
M
Zhao
Yu Xia
YX
Zhang
Cheng
C
Zhang
Yun
Y
D000284:Administration, Oral; D000818:Animals; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007378:Interleukins / Q000097:blood; D008055:Lipids / Q000097:blood*; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D019007:P-Selectin / Q000097:blood; D011817:Rabbits; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D014463:Ultrasonography
D015415:Biomarkers; D018932:Chemokine CCL2; D007378:Interleukins; D008055:Lipids; D019007:P-Selectin; D002097:C-Reactive Protein; D020781:Matrix Metalloproteinase 1; D020123:Sirolimus