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Article

Angiotensin‑(1‑7) stimulates cholesterol efflux from angiotensin II‑treated cholesterol‑loaded THP‑1 macrophages through the suppression of p38 and c‑Jun N‑terminal kinase signaling

  • Authors:
    • Hui‑Yu Yang
    • Yun‑Fei Bian
    • Chuan‑Shi Xiao
    • Bin Liang
    • Nana Zhang
    • Fen Gao
    • Zhi‑Ming Yang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
  • Pages: 1387-1392
    |
    Published online on: March 13, 2015
       https://doi.org/10.3892/mmr.2015.3484
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Abstract

Angiotensin II (Ang II) and Ang‑(1‑7) are key effector peptides of the renin‑angiotensin system. The present study aimed to investigate the effects of Ang‑(1‑7) on Ang II‑stimulated cholesterol efflux and the associated molecular mechanisms. Differentiated THP‑1 macrophages were treated with Ang II (1 µM) and/or Ang‑(1‑7) (10 and 100 nM) for 24 h and the cholesterol efflux and gene expression levels were assessed. Pharmacological inhibition of peroxisome proliferator‑activated receptor (PPAR)γ and mitogen‑activated protein kinases (MAPKs) were performed to identify the signaling pathways involved. The results demonstrated that Ang II significantly inhibited the cholesterol efflux from cholesterol‑loaded THP‑1 macrophages. Treatment with Ang‑(1‑7) led to a dose‑dependent restoration of cholesterol efflux in the Ang II‑treated cells. The co‑treatment with Ang‑(1‑7) and Ang II significantly increased the expression levels of adenosine triphosphate (ATP)‑binding cassette (ABC)A1 and ABCG1 compared with treatment with Ang II alone. This was coupled with increased expression levels of PPARγ and liver X receptor (LXR)α. The pharmacological inhibition of PPARγ significantly (P<0.05) eliminated the Ang‑(1‑7)‑mediated induction of ABCA1 and ABCG1 mRNA expression. Treatment with Ang‑(1‑7) caused the inactivation of c‑Jun N‑terminal kinases (JNK) and p38 MAPK signaling in the Ang II‑treated THP‑1 macrophages. In addition, the inhibition of JNK or p38 MAPK signaling using specific pharmacological inhibitors mimicked the Ang‑(1‑7)‑induced expression of PPARγ and LXRα. In conclusion, the data demonstrated that treatment with Ang‑(1‑7) promoted cholesterol efflux in Ang II‑treated THP‑1 macrophages, partly through inactivation of p38 and JNK signaling and by inducing the expression of PPARγ and LXRα. Ang (1‑7) may, therefore, have therapeutic benefits for the treatment of atherosclerosis.
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Copy and paste a formatted citation
Spandidos Publications style
Yang HY, Bian YF, Xiao CS, Liang B, Zhang N, Gao F and Yang ZM: Angiotensin‑(1‑7) stimulates cholesterol efflux from angiotensin II‑treated cholesterol‑loaded THP‑1 macrophages through the suppression of p38 and c‑Jun N‑terminal kinase signaling. Mol Med Rep 12: 1387-1392, 2015.
APA
Yang, H., Bian, Y., Xiao, C., Liang, B., Zhang, N., Gao, F., & Yang, Z. (2015). Angiotensin‑(1‑7) stimulates cholesterol efflux from angiotensin II‑treated cholesterol‑loaded THP‑1 macrophages through the suppression of p38 and c‑Jun N‑terminal kinase signaling. Molecular Medicine Reports, 12, 1387-1392. https://doi.org/10.3892/mmr.2015.3484
MLA
Yang, H., Bian, Y., Xiao, C., Liang, B., Zhang, N., Gao, F., Yang, Z."Angiotensin‑(1‑7) stimulates cholesterol efflux from angiotensin II‑treated cholesterol‑loaded THP‑1 macrophages through the suppression of p38 and c‑Jun N‑terminal kinase signaling". Molecular Medicine Reports 12.1 (2015): 1387-1392.
Chicago
Yang, H., Bian, Y., Xiao, C., Liang, B., Zhang, N., Gao, F., Yang, Z."Angiotensin‑(1‑7) stimulates cholesterol efflux from angiotensin II‑treated cholesterol‑loaded THP‑1 macrophages through the suppression of p38 and c‑Jun N‑terminal kinase signaling". Molecular Medicine Reports 12, no. 1 (2015): 1387-1392. https://doi.org/10.3892/mmr.2015.3484
Copy and paste a formatted citation
x
Spandidos Publications style
Yang HY, Bian YF, Xiao CS, Liang B, Zhang N, Gao F and Yang ZM: Angiotensin‑(1‑7) stimulates cholesterol efflux from angiotensin II‑treated cholesterol‑loaded THP‑1 macrophages through the suppression of p38 and c‑Jun N‑terminal kinase signaling. Mol Med Rep 12: 1387-1392, 2015.
APA
Yang, H., Bian, Y., Xiao, C., Liang, B., Zhang, N., Gao, F., & Yang, Z. (2015). Angiotensin‑(1‑7) stimulates cholesterol efflux from angiotensin II‑treated cholesterol‑loaded THP‑1 macrophages through the suppression of p38 and c‑Jun N‑terminal kinase signaling. Molecular Medicine Reports, 12, 1387-1392. https://doi.org/10.3892/mmr.2015.3484
MLA
Yang, H., Bian, Y., Xiao, C., Liang, B., Zhang, N., Gao, F., Yang, Z."Angiotensin‑(1‑7) stimulates cholesterol efflux from angiotensin II‑treated cholesterol‑loaded THP‑1 macrophages through the suppression of p38 and c‑Jun N‑terminal kinase signaling". Molecular Medicine Reports 12.1 (2015): 1387-1392.
Chicago
Yang, H., Bian, Y., Xiao, C., Liang, B., Zhang, N., Gao, F., Yang, Z."Angiotensin‑(1‑7) stimulates cholesterol efflux from angiotensin II‑treated cholesterol‑loaded THP‑1 macrophages through the suppression of p38 and c‑Jun N‑terminal kinase signaling". Molecular Medicine Reports 12, no. 1 (2015): 1387-1392. https://doi.org/10.3892/mmr.2015.3484
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