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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 ; 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.

. Prediction of atherosclerotic plaque ruptures with high-frequency ultrasound imaging and serum inflammatory markers. Am J Physiol Heart Circ Physiol 293: H2836-H2844, 2007. First published August 17, 2007; doi:10.1152/ajpheart.00472.2007.-Atherosclerotic plaque rupture and thrombosis are the main causes of acute coronary syndrome. In the present study, we investigated whether ultrasound imaging and inflammatory parameters are predictive of plaque rupture in a newly established animal model. We developed a rabbit model for plaque rupture by locally delivering recombinant p53 adenovirus to plaques in rabbits fed a high-cholesterol diet for 10 wk, and plaque rupture was triggered using Chinese Russell's viper venom and histamine. We found that 81.1% of rabbits transfected with p53 (n ϭ 37) had the ruptured plaques, which was significantly higher than results in rabbits transfected with the control vector (26.3%, n ϭ 38; P Ͻ 0.001). Among measured biomarkers, high-sensitive C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were significantly different between rabbits with and without ruptured plaques. Using high-frequency duplex and intravascular ultrasound imaging techniques, we obtained a list of parameters. With the multivariate logistic regression model, we identified that plaque eccentric index, plaque area, high-sensitive C-reactive protein, and corrected integrated backscatter intensity were significant predictors of plaque rupture, with odds ratios of 7.056 [95% confidence interval (CI): 1.958, ϳ25.430], 1.942 (95% CI: 1.058, ϳ3.564), 1.025 (95% CI: 1.007, ϳ1.043), and 0.856 (95% CI: 0.775, ϳ0.946), respectively. Localized p53 overexpression technique induces plaque rupture, and the combined measurement of ultrasound and biochemical markers is a valuable tool in predicting plaque rupture. atherosclerosis; vulnerable plaque; p53; biomarkers ATHEROSCLEROTIC PLAQUE RUPTURE is the major cause of acute coronary syndrome (ACS) (4, 9).A plaque with a thin cap, a large lipid core, and abundant activated macrophages has been generally regarded as unstable and vulnerable to rupture. Although early detection or prevention would be the only way to reduce the risk of this catastrophic life-threatening event, there is frustratingly little progress in either. Lack of suitable animal models has considerably hampered the research progress in understanding molecular events occurring in the development of plaque rupture. It remains unclear what morphological and biochemical features will best predict plaque rupture and which in vivo diagnostic technologies would reliably predict the pathological and clinical courses of an unstable plaque. Currently, most factors found to be associated with plaque rupture and ensuing thrombosis in ACS are derived from cross-sectional retrospective rather than prospective studies (3,22,29).Recently, a variety of imaging techniques, including highfrequency duplex ultrasound, intravascular ultrasound (IVUS), IVUS elastography, coronary ...

Short-term pretreatment with a high dose of atorvastatin significantly reduces procedural myocardial injury in early PCI.