title: Up-regulating PPAR-γ expression and NO concentration, and down-regulating PAI-1 concentration in a rabbit atherosclerotic model: the possible antiatherogenic and antithrombotic effects of atorvastatin.
abstract: We investigated the effect of atorvastatin on the plasma concentration of plasminogen activator inhibitor-1 (PAI-1) and nitric oxide (NO) in a rabbit model, and the relationship between these effects and peroxisome proliferator-activated receptor γ (PPAR-γ). In our experiments, 24 male Japanese rabbits were divided into 3 groups: the high-cholesterol diet group (the high-C group), the high-cholesterol diet plus atorvastatin group (the atorvastatin group), and the normal diet group (the control group). All rabbits were killed after a 16-week feeding. The expression of PPAR-γ and the plasma concentrations of NO and PAI-1 were evaluated by an immunohistochemical assay while the level of the plasma lipid profile was measured using a commercially available kit. The atorvastatin not only reduces the plasma levels of the total cholesterol (TC) and the low-density lipoprotein cholesterol (LDL-C), but also increases the expression of PPAR-γ and the concentration of NO in comparison to the control group [16.11 ± 2.35% vs 7.68 ± 1.04%; 249.30 ± 27.90 vs 179.12 ± 28.51 (μml/L), p<0.05 respectively]. In addition, the concentration of PAI-1 in the atorvastatin group is lower than that in the control group (0.11 ± 0.01A vs 0.14 ± 0.02A, p<0.05). The changes of PAI-1 and NO in the atorvastatin group are in good accordance to that of PPAR-γ. Results show that atorvastatin significantly up-regulates the expression of nuclear transcription factor, namely PPAR-γ, and induces the changes of the other two factors, which might provide mechanisms for the antiatherosclerotic and antithrombotic effects of atorvastatin.
authors.affiliation: Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Jian Jun
authors.initials: JJ
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.forename: Xue Yu
authors.initials: XY
authors.lastname: Li
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D000069059:Atorvastatin; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D047495:PPAR gamma / Q000096:biosynthesis*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D005343:Fibrinolytic Agents; D006538:Heptanoic Acids; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; D011758:Pyrroles; D009569:Nitric Oxide; D000069059:Atorvastatin