Effect And Mechanism Of PEDF On The Stability Of Atherosclerotic Plaque

ObjectiveAtherosclerosis is an inflammatory disease promoted by hypercholesterolemia. Pigment epithelium-derived factor (PEDF) is a multifunctional cytokine which has the ability of anti-angiogenesis, anti-oxidation, anti-inflammation. Recent studies reported that PEDF plays a vital role in cardiovascular disease (CVD), but opinions of the function of PEDF and the mechanism in this process are divergent. The aim of this study is to examine the effect of PEDF on the stability of atherosclerotic plaque and to explore the mechanism involved.Methods and ResultsThe model of atherosclerotic plaque in apolipoprotein E (ApoE)-knockout mice and the lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used to evaluate anti-inflammatory activities of PEDF both in vivo and in vitro. PEDF overexpression improved atherosclerotic plaque stability in ApoE-Knockout mice. The expression of inflammatory factors (interleukin-1?[IL-1?], interleukin-6 [IL-6], tumor necrosis factor-? [TNF-?], monocyte chemotactic protein-1[MCP-1] and matrix metalloproteinase [MMP-9]) detected by western blot and immunohistochemistry were significantly decreased with PEDF treatment in vivo and in vitro.PEDF had no significant effect on MMP-2 expression. The inhibitory effect of PEDF on inflammatory response in macrophages induced by lipopolysaccharide was attenuated by PPAR-y specific antagonist (GW9662). In addition, PEDF significantly decreased the expression of phosphorylated ERK-MAPK and p38-MAPK. However, no significant difference in phosphorylated JNK-MAPK was observed between PEDF and control. GW9662 partly reversed the PEDF-mediated depression of phosphorylated ERK- and p38-MAPK.ConclusionsPEDF enhances the stability of atherosclerotic plaque by inhibiting the expression of inflammatory factors, which is dependent on PPAR-?. ERK-MAPK and p38-MAPK, but not JNK-MAPK, are involved in the anti-inflammatory effect of PEDF regulated by PPAR-?.As the development of social living standards, the morbidity of obesity is increasing year by year, affecting the physiological function of various tissues and organs in the body which can lead to the occurrence and development of many diseases. The brown fat has the function of speeding up metabolism and increasing the energy dissipation which is different from the white fat, and recent research shows the brown fat exists in major. Therefore, increasing the content of brown fat to increase energy consumption has become a new research direaction. Ginsenoside Rbl is a multifunctional panaxadiol saponin which play a role in lipid metabolism, but the mechanism of this process is not clear. Our research showed that the weight of these obese mice decreased after the administration of Rb1, meanwhile, the expression of UCP-1 incresed in 3T3-L1 cells after the adiministration of Rb1. We measured the changes in GPDH by WB and IHC. We tested the changed of blood lipid and the activity of mitochondrial. We draw the conclusion that Rb1 decreses the weight of obese individuals by increasing the content of brown fat through regulating PPAR-y.