Backgrounds: We recently reported that Naoxintong (NXT), a China Food
and Drug Administration (FDA)-approved cardiac medicine, could reduce the plaque
size, but the underlying mechanism remains elusive now.
Objective: In this study, we investigated the effects of NXT on foam cell accumulation
both in vivo and in vitro and explored related mechanisms.
Method: THP-1 cells and bone marrow-derived macrophages were incubated with
oxidized low-density lipoprotein (ox-LDL) with/without Naoxintong. ApoE-/- mice fed an
atherogenic diet were administered to receive NXT for eight weeks. Macrophage-derived
foam cell formation in plaques was measured by immunohistochemical staining.
Expression of proteins was evaluated by Western blot. Lentivirus was used to
knockdown PPARα in THP-1 cells.
Results: After NXT treatment, foam cell accumulation was significantly reduced in
atherosclerotic plaques. Further investigation revealed that oxidized low-density
lipoprotein (ox-LDL) uptake was significantly decreased and expression of scavenger
receptor class A (SR-A) and class B (SR-B and CD36) was significantly downregulated
post-NXT treatment. On the other hand, NXT increased cholesterol efflux and
upregulated ATP-binding cassette (ABC) transporters (ABCA-1 and ABCG-1) in
macrophages. Above beneficial effects of NXT were partly abolished after lentiviral
knockdown of PPARα.
Conclusion: Our findings suggest that NXT could retard atherosclerosis by inhibiting
foam cell formation through reducing ox-LDL uptake and enhancing cholesterol efflux
and above beneficial effects are partly mediated through PPARα pathway.