OBJECTIVE: The 5-lipoxygenase catalyzed formation of leukotriene 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 cysLT1R 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 cysLT1R was significantly 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.
OBJECTIVE: The 5-lipoxygenase catalyzed formation of leukotrienelipid 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 cysLT1R 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 cysLT1R was significantly 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.
Authors: Stuart G Snowden; Dmitry Grapov; Magnus Settergren; Fabio Luiz D'Alexandri; Jesper Z Haeggström; Oliver Fiehn; Tuulia Hyötyläinen; Theresa L Pedersen; John W Newman; Matej Orešič; John Pernow; Craig E Wheelock Journal: Circ Cardiovasc Genet Date: 2014-12
Authors: A Millon; S D Dickson; A Klink; D Izquierdo-Garcia; J Bini; E Lancelot; S Ballet; P Robert; J Mateo de Castro; C Corot; Z A Fayad Journal: Atherosclerosis Date: 2013-03-26 Impact factor: 5.162
Authors: Rafael I Jaén; Sergio Sánchez-García; María Fernández-Velasco; Lisardo Boscá; Patricia Prieto Journal: Front Immunol Date: 2021-04-23 Impact factor: 7.561
Authors: Francesca Colazzo; Paolo Gelosa; Elena Tremoli; Luigi Sironi; Laura Castiglioni Journal: Mediators Inflamm Date: 2017-08-28 Impact factor: 4.711