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Curr Mol Med. 2018;18(10):698-710. doi: 10.2174/1566524019666190207143207.

Naoxintong Retards Atherosclerosis by Inhibiting Foam Cell Formation Through Activating Pparα Pathway.

Author information

1
Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
2
Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
3
Department of Pathology, LiShui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical College, ZheJiang, China.
4
Shandong Buchang Pharmaceutical Co., Ltd, Shandong, China.

Abstract

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.

KEYWORDS:

Naoxintong; PPARα; atherosclerosis; foam cell; macrophage.

PMID:
30734676
PMCID:
PMC6463403
DOI:
10.2174/1566524019666190207143207
[Indexed for MEDLINE]
Free PMC Article

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