However, XYS granules inhibited the development of atherosclerotic lesion, with down-regulation of GC, TC, TG, HDL-C, ox-LDL, LDL-C, IFN-γ, IL-6, IL-1β, and TNF-α measured by ELISA method; XYS inhibited the expressions of GR, CD36, HSP27/60/90, and induced ABCA1 in atherosclerotic mice, which was measured by qPCR and Western blot, which showed similar effect as positive control RU 38486 did.
Lastly, in LPS-challenged apoE-/- mice, apigenin administration augmented ABCA1 expression, decreased the contents of macrophages and smooth muscle cells in atherosclerotic lesion, reduced miR-33, TLR-4, and NF-κB p65 levels, improved plasma lipid profile and relieved inflammation, which results in less atherosclerotic lesion size.
These results demonstrate that HIF-1beta availability determines ABCA1 expression and cholesterol efflux in macrophages under hypoxia and may contribute to the interpersonal variability of atherosclerotic lesion progression.
ABCA1 expression is reduced in cultured model intimal and human atherosclerotic lesion SMCs, suggesting that reduced ABCA1 activity contributes to smooth muscle foam cell formation in the intima.
The increase of ABCA1 in monocytes in association with blood oxLDL prior to atherosclerotic lesion formation and the association of higher ABCA1 with higher plaque complexity suggests that ABCA1 is an early biomarker of atherosclerosis.Studies in humans are warranted.
However, after 12 weeks, the mean atherosclerotic lesion area in ABCA1 BAC --> LDLr-/- mice remained only 164+/-15x10(3) microm2 (P=0.0008) compared with 513+/-56x10(3) microm2 in controls (3.1-fold lower).