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

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

Volume: 18 Issue: 10

Author(s): Zeng Wang, Huairui Shi, Huan Zhao, Zhen Dong, Buchang Zhao, Xinyu Weng, Rongle Liu, Xiao Li, Kai Hu, Yunzeng Zou, Aijun Sun*Junbo Ge *

Affiliation:

• Institutes of Biomedical Sciences, Fudan University, Shanghai 200032,China

• Institutes of Biomedical Sciences, Fudan University, Shanghai 200032,China

Keywords: Naoxintong, atherosclerosis, macrophage, foam cell, PPARα.

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.

Cite this article as:

Wang Zeng , Shi Huairui, Zhao Huan , Dong Zhen, Zhao Buchang, Weng Xinyu, Liu Rongle, Li Xiao , Hu Kai , Zou Yunzeng , Sun Aijun *, Ge Junbo *, Naoxintong Retards Atherosclerosis by Inhibiting Foam Cell Formation Through Activating Pparα Pathway, Current Molecular Medicine 2018; 18 (10) . https://dx.doi.org/10.2174/1566524019666190207143207