Atorvastatin Reduces Plaque Vulnerability in an Atherosclerotic Rabbit Model by Altering the 5-Lipoxygenase Pathway

摘要

Objective: The 5-lipoxygenase catalyzed formation of leu-kotriene lipid mediators is a mediator for inflammatory response in arteries. The present study investigated the relationship between atorvastatin and the 5-lipoxygenase pathway in an atherosclerotic rabbit model. Methods: Thirty male New Zealand White Rabbits were randomized into negative control, positive control and atorvastatin groups. At week 4, the rabbits were subjected to carotid balloon-dilation injury or carotid balloon-dilation injury, followed by treatment with atorvastatin. At week 12, all the animals were sacrificed. Plasma lipids, LTD_4, and 15-epi-lipoxin A_4 were measured using the enzymatic endpoint method and ELISA, respectively. RT-PCR was performed to detect the gene expression of 5-lipoxygenase-activating protein and cysLTIR in rabbit carotid arteries. Finally, histological analysis was used to evaluate the pathophysiological changes of rabbit carotid arteries. Results: The results showed atorvastatin markedly lowered serum lipids and LTD_4 levels compared with the control group. Similarly, mRNA expression of 5-lipoxygenase-activating protein and cysLTIR was significant-ly inhibited by atorvastatin. Decreased carotid plaque instability was evident in atorvastatin-treated animals, as demonstrated by a thickened elastic layer, less neointima hyperplasia and macrophage proliferation. Conclusions: Atorvastatin may stabilize carotid plaque by regulating the 5-lipoxygenase pathway in atherosclerotic rabbits and delay the progression of atherosclerosis by exerting anti-inflammatory effects.