The atherogenic effects of serum amyloid A are potentially mediated via inflammation and apoptosis.
OBJECTIVE
The mechanism through which SAA contributes to the pathogenesis of atherosclerosis remains unclear. The objective of this study was therefore to determine whether SAA plays a role in the onset of atherosclerosis via inflammatory and apoptotic pathways.


METHODS
An array of experiments, including cell cultures, MTT assays, quantitative real-time PCR and Western blotting, were carried out in order to assess the effects of human recombinant SAA on NF-κB activation and the role of NF-κB in the onset of SAA-induced inflammation and apoptosis.


RESULTS
We found that SAA (80μg/mL) induced 3.5- to 37.8-fold increases in the expression of targets known to play important roles in the initiation and progression of atherosclerosis (i.e., ICAM-1, MCP-1, MMP-9 and TF) via NF-κB regulation within one hour after exposure. RAW264.7 cells treated with increasing doses of SAA showed regulation of apoptotic targets and a dose-dependent reduction in cell viability, with 69% cell viability observed following exposure to 80μg/mL of SAA for 24 hours.


CONCLUSIONS
Our results suggest that SAA contributes to the pathogenesis of atherosclerosis via both inflammatory and apoptotic mechanisms.
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore.
Si-Zhen
SZ
Tan
Delicia Shu-Qin
DS
Ooi
Han-Ming
HM
Shen
Chew-Kiat
CK
Heng
D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*
D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein