Inhibitory effect of apolipoprotein A-I on matrix metalloproteinase-2 expression <italic>in vivo</italic> and <italic>in vitro</italic>

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 a/g (PPAR a/g), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-kB) expressions in atherosclerotic rabbit models using immunohistochemical methods. The results showed that the expressions of MMP-2, COX-2, and NF-kB were decreased in aortas of atherosclerotic rabbits treated with apoA-I, while PPAR a/g 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 a/g, and COX-2 were then determined using reverse-transcription polymerase chain reaction, and protein expression of PPAR g, NF-kB were detected by western blot analysis. The levels of MMP-2 and PPAR a 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-kB were decreased, while PPAR a/g 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 a/g, COX-2, and NF-kB 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.

CRISPR/dCas9 Transcriptional Activation of Endogenous Apolipoprotein AI and Paraoxonase 1 in Enterocytes Alleviates Endothelial Cell Dysfunction

“…Therefore, an explanation for the mutual stimulation of ApoAI and PON1, and for their effect on ABCA1 protein expression could be the increase of the levels of their transcriptional activators PPARγ, LXRs, and SIRT1. Our results are supported by the group of Wang et al who published data showing that human-apoAI treatment upregulates PPARγ expression in THP-1 macrophages [ 38 ]. Moreover, very recently published results show that lentiviral-induced human-PON1 overexpression in the liver of SR-BI deficient mice upregulates LXR and its downstream genes, including ApoAI and ABCA1 [ 39 ].…”

Peroxisome Proliferator-Activated Receptor α in Lipid Metabolism and Atherosclerosis

“…Its expression is significantly downregulated in IL-1β-treated human macrophages in the presence of a specific PPARα agonist GW647 [121]. In addition, rabbit macrophages treated with apo A-I display a marked decrease of MMP-2 levels due to elevated PPARα expression [122]. Thus, PPARα activation in macrophages may contribute to the stability of atherosclerotic plaques by enhancing collagen contents via downregulation of MMP-9, MMP-12, and MMP-2.…”

Cholesterol Efflux: Does It Contribute to Aortic Stiffening?

“…This is achieved by diminishing vascular collagen deposition, normalizing altered elastin structure, and decreasing connective tissue growth factor gene expression [ 66 ]. An inhibitory effect of Apo A1 on COX-2 expression has also been observed [ 67 , 68 ]. Cholesterol efflux plays a role in the protection of aortic stiffness development by enhancing endothelial function, as well as inhibiting VSMC proliferation and inflammatory response.…”