Zeng Wang, Huairui Shi, Huan Zhao, Zhen Dong, Buchang Zhao, Xinyu Weng, Rongle Liu, Xiao Li, Kai Hu, Yunzeng Zou, Aijun Sun* and Junbo Ge * Pages 698 - 710 ( 13 )
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. </P><P> Objective: In this study, we investigated the effects of NXT on foam cell accumulation both in vivo and in vitro and explored related mechanisms. </P><P> 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. </P><P> 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. </P><P> 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 PPARĪ± pathway.
Naoxintong, atherosclerosis, macrophage, foam cell, PPARα.
Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, Department of Pathology, LiShui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical College, ZheJiang, Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, Shandong Buchang Pharmaceutical Co., Ltd, Shandong, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032