Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/29564
Title: Serum Amyloid A (SAA) and cholesterol efflux -- a mechanistic study
Authors: LI HONGZHE
Keywords: serum amyloid A, coronary artery disease, cholesterol efflux, peroxisome proliferator-activated receptor γ
Issue Date: 17-Jan-2011
Source: LI HONGZHE (2011-01-17). Serum Amyloid A (SAA) and cholesterol efflux -- a mechanistic study. ScholarBank@NUS Repository.
Abstract: Coronary artery disease (CAD) most often results from atherosclerosis, a progressive condition characterized by the accumulation of lipids and fibrous elements in the large arteries. Many inflammatory proteins are elevated in this process and correlated with future coronary events. One of such inflammatory proteins is serum amyloid A (SAA). SAA is an acute phase protein whose level of expression increases markedly during bacterial infection, tissue damage, and inflammation. The potential beneficial roles of SAA include its involvement in reverse cholesterol transport and possibly extracellular lipid deposition at sites of inflammation and tissue repair. It is an attractive therapeutic target for the treatment of atherosclerosis. Peroxisome proliferator-activated receptor ? (PPAR?) plays a major regulatory role in adipogenesis and in the expression of genes involved in lipid metabolism. Activation of PPAR? leads to multiple changes in gene expression, some of which are believed to be atherogenic while others are antiatherogenic. In this study, we investigated the effects of SAA on PPAR? activation and its downstream target gene expression profiles in HepG2 cells. We demonstrated that SAA could activate PPAR? transcriptional activity. Preincubation of HepG2 cells with SAA enhanced the efflux of cholesterol to HDL and apoA-I. In addition, SAA increased the level of intracellular 15-deoxy-?12,14-prostaglandin J2 (15d-PGJ2), which is a potent natural ligand for PPAR?. Our data suggested that SAA activated PPAR? through extracellular signal-regulated kinase 1/2 (ERK1/2) and NF-?B dependent COX-2 expression. Furthermore, SAA-induced cholesterol efflux was suppressed when the ERK1/2 pathway or COX-2 was inhibited. Overall, our study has established, for the first time, a relationship between SAA and PPAR?. Additionally, the data from our study has also provided new insights into the role of SAA in cholesterol efflux.
URI: http://scholarbank.nus.edu.sg/handle/10635/29564
Appears in Collections:Ph.D Theses (Open)

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