Abstract
Aim: 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.
