title: Inhibitory effect of apolipoprotein A-I on matrix metalloproteinase-2 expression in vivo and in vitro.
abstract: In the present study, we investigated the effects of apolipoprotein A-I (apoA-I) on matrix metalloproteinase-2 (MMP-2) expression in vivo and in vitro. First, we detected the effects of apoA-I on aorta MMP-2, peroxisome proliferator-activated receptor α/γ (PPAR α/γ), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) expressions in atherosclerotic rabbit models using immunohistochemical methods. The results showed that the expressions of MMP-2, COX-2, and NF-κB were decreased in aortas of atherosclerotic rabbits treated with apoA-I, while PPAR α/γ expression was increased. Then, we chose the important inflammation cells, macrophages to testify those effects in vitro. Macrophages were divided into six groups and treated with different concentrations of apoA-I, the mRNA expressions of MMP-2, PPAR α/γ, and COX-2 were then determined using reverse-transcription polymerase chain reaction, and protein expression of PPAR γ, NF-κB were detected by western blot analysis. The levels of MMP-2 and PPAR α in cultured supernatants were determined using enzyme-linked immunosorbent assays. Interestingly, the in vitro results were similar to the results of the in vivo study. After incubation with apoA-I for 24 h, the expressions of MMP-2, COX-2, and NF-κB were decreased, while PPAR α/γ expression was increased. In consideration of their particular roles in the process of making plaque stable in vivo and in vitro, we speculate that the inhibitory effect of apoA-I on MMP-2 expression may have a close relationship with the effects of apoA-I on PPAR α/γ, COX-2, and NF-κB expressions. Although further research is needed to clarify the underlying mechanisms of these effects, our findings provide a novel insight into the anti-atherosclerotic plaque rupture effects of apoA-I.
authors.affiliation: Department of Pharmacology,  Fudan University, Shanghai 201203,  China.
authors.forename: Weina
authors.initials: W
authors.lastname: Wang
authors.forename: Xunlong
authors.initials: X
authors.lastname: Shi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Meiqing
authors.initials: M
authors.lastname: Feng
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D050197:Atherosclerosis; D002470:Cell Survival; D051546:Cyclooxygenase 2 / Q000378:metabolism; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011817:Rabbits
chemical_list: D016632:Apolipoprotein A-I; D016328:NF-kappa B; D047493:PPAR alpha; D047495:PPAR gamma; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2