-Coumaric acid modulates cholesterol efflux and lipid accumulation and inflammation in foam cells.

BACKGROUND/OBJECTIVES: Atherosclerosis is a primary cause of cardiovascular disease associated with inflammation and lipid metabolism disorders. The accumulation of cholesterol-containing macrophage foam cells characterizes the early stages. The -coumaric acid (CA) contained in vegetables may have various physiological activities. The inhibitory effect of -CA on foam cell creation in THP-1 macrophages needs clarification. In this study, we explored the impact of -CA on foam cells by co-treatment with oxidized low-density lipoprotein (ox-LDL) and lipopolysaccharides (LPS), mimicking the development of atherosclerosis and studied the regulation of its underlying mechanisms.

MATERIALS/METHODS: THP-1 cells differentiated by phorbol 12-myristate 13-acetate (1 μM) for 48 h and treated in the absence or presence of -CA for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability. Oil red O staining allowed us to observe lipid accumulation. Western blotting and quantitative polymerase chain reactions quantified corresponding proteins and mRNA.

RESULTS

Ox-LDL and LPS for 24 h enhanced the lipid accumulation using Oil red O in treated foam cells. By contrast, -CA treatment inhibited lipid accumulation. -CA significantly upregulated cholesterol efflux-related genes such as ATP binding cassette transporter A1, liver-X-receptor α and peroxisome proliferator-activated receptor gamma expression. Moreover, -CA decreased lipid accumulation-related gene such as lectin-like oxidized low-density lipoprotein receptor-1, cluster of differentiation 36 and scavenger receptor class A1 expression. Combined ox-LDL and LPS increased nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and pro-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin [IL]-6) activation and expression compared with untreated. -CA suppressed this increased expression of NF-κB and COX-2, TNF-α and IL-6.

CONCLUSION

-CA may play a vital role in atherosclerosis inhibition and protective effects by suppressing lipid accumulation and foam cell creation by increasing cholesterol efflux and can be potential agents for preventing atherosclerosis.