Nifedipine enhances cholesterol efflux in RAW264.7 macrophages.

PURPOSE: Studies have shown that nifedipine protects against atherosclerotic progression, but its underlying mechanisms remain unclear. In this study, we examined if nifedipine increases macrophage cholesterol efflux, a pathway known to inhibit atherogenesis.

METHODS

We evaluated the ability of different doses of nifedipine to affect cholesterol efflux in RAW264.7 macrophages and its relationship with mRNA and protein levels of several well-characterized proteins involved in cholesterol efflux, including ABCA1, ABCG1, SR-BI and LXRα, using quantitative real-time PCR, Western blotting, and siRNA techniques.

RESULTS

Nifedipne at 1, 10, and 100 nmol/L increased apoA-I-mediated cholesterol efflux from 2.55 % to 5.65 %, 6.20 %, and 6.10 %, as well as HDL-mediated cholesterol efflux from 31.0 % to 42.5 %, 46.0 %, and 43.5 %, respectively, in RAW264.7 macrophages (p < 0.05), which was associated with increased mRNA expression levels of ABCA1, ABCG1, SR-BI, and LXRα (405 %, 381 %, 336 %; 890 %, 960 %, 1002 %; 285 %, 325 %, 336 %; 482 %, 445 %, 405 %, respectively, p < 0.05), and with increased protein levels of ABCA1, ABCG1, SR-BI, and LXRα (428 %, 492 %, 361 %; 288 %, 331 %, 365 %; 283 %, 320 %, 505 %; 581 %, 678 %, 608 %, respectively, p < 0.05). SiRNA-mediated silencing of LXRα revealed that LXRα was involved in these increases and the enhanced cholesterol efflux.

CONCLUSION

Nifedipine may protect against atherosclerosis partly by promoting macrophage cholesterol efflux through the stimulation of LXRα-dependent expression of ABCA1, ABCG1, and SR-BI.