title: Atorvastatin inhibits the 5-lipoxygenase pathway and expression of CCL3 to alleviate atherosclerotic lesions in atherosclerotic ApoE knockout mice.
abstract: BACKGROUND
  The 5-lipoxygenase (5-LO) pathway and the chemokine CCL3 are involved in the inflammatory processes of atherosclerosis. Statins have shown cholesterol-independent pleiotropic effects on antiimmune and antiinflammatory responses in atherosclerosis. We postulated that this effect may be associated with the 5-LO pathway and CCL3.
  
  
  RESULTS
  ApoE knockout mice were randomized into control group (normal diet), atherosclerosis group (high-cholesterol diet), and atorvastatin group (high-cholesterol diet and atorvastatin). Sixteen weeks later, aortic roots were stained with hematoxylin and eosin. Total cholesterol and low-density lipoprotein cholesterol were measured by the enzymatic methods. The gene and protein expressions of 5-LO and CCL3 were detected separately through real-time reverse transcription polymerase chain reaction and western blotting analyses. The serum levels of leukotriene B4 and leukotriene D4 were measured by enzyme-linked immunosorbent assay. All mice have atherosclerotic plaques, mice in the control group have only tiny atherosclerotic plaques, but mice in the atherosclerosis group and atorvastatin group have typical atherosclerotic plaques. The corrected plaque areas (plaque area/luminal area) of the aortas of mice in the atorvastatin group were significantly decreased compared with those of the atherosclerosis group. The serum cholesterol levels of the atorvastatin group were not of significant difference compared with those of the atherosclerosis group. The gene and protein expressions of 5-LO and CCL3 in the aortas, as well as the serum levels of leukotriene B4 and leukotriene D4 in atorvastatin group, were markedly reduced compared with those of the atherosclerosis group.
  
  
  CONCLUSIONS
  These data suggested that atorvastatin significantly alleviated atherosclerotic lesions by inhibiting the 5-LO pathway and down regulating the expression of CCL3 in ApoE-/- mice.
authors.affiliation: Department of Cardiology, Kunming General Hospital of Chengdu Military Command, Kunming, China. doctorylixia@yahoo.com.cn
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Yang
authors.forename: Xu-Hua
authors.initials: XH
authors.lastname: Heng
authors.forename: Rui-Wei
authors.initials: RW
authors.lastname: Guo
authors.forename: Yan-Kun
authors.initials: YK
authors.lastname: Si
authors.forename: Feng
authors.initials: F
authors.lastname: Qi
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000069059:Atorvastatin; D054405:Chemokine CCL3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000009:adverse effects; D015536:Down-Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015289:Leukotrienes / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000517:prevention & control*; D011758:Pyrroles / Q000627:therapeutic use*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015289:Leukotrienes; D011758:Pyrroles; D000069059:Atorvastatin; D001094:Arachidonate 5-Lipoxygenase