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The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice

  • Authors:
    • Ying Yu
    • Zhaohua Cai
    • Mingli Cui
    • Peng Nie
    • Zhe Sun
    • Shiqun Sun
    • Shichun Chu
    • Xiaolei Wang
    • Liuhua Hu
    • Jing Yi
    • Linghong Shen
    • Ben He
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China, Department of Cell Biology, Key Laboratory of the Education Ministry for Cell Differentiation and Apoptosis, Institutes of Medical Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China
    Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1547-1555
    |
    Published online on: October 14, 2015
       https://doi.org/10.3892/ijmm.2015.2375
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Abstract

Shear stress, particularly low and oscillatory shear stress, plays a critical pathophysiological role in vascular remodeling-related cardiovascular diseases. Growing evidence suggests that the orphan nuclear receptor Nur77 [also known as TR3 or nuclear receptor subfamily 4, group A, member 1 (NR4A1)] is expressed in diseased human vascular tissue and plays an important role in vascular physiology and pathology. In the present study, we used a mouse model of flow-dependent remodeling by partial ligation of the left common carotid artery (LCCA) to define the exact role of Nur77 in vascular remodeling induced by low shear stress. Following vascular remodeling, Nur77 was highly expressed in neointimal vascular smooth muscle cells (VSMCs) in the ligated carotid arteries. The reactive oxygen species (ROS) levels were elevated in the remodeled arteries in vivo and in primary rat VSMCs in vitro following stimulation with platelet-derived growth factor (PDGF). Further in vitro experiments revealed that Nur77 expression was rapidly increased in the VSMCs following stimulation with PDGF and H2O2, whereas treatment with N-acetyl cysteine (NAC, a ROS scavenger) reversed the increase in the protein level of Nur77 induced by H2O2. Moreover, Nur77 overexpression markedly inhibited the proliferation and migration of VSMCs, induced by PDGF. Finally, to determine the in vivo role of Nur77 in low shear stress-induced vascular remodeling, wild-type (WT) and Nur77-deficient mice were subjected to partial ligation of the LCCA. Four weeks following surgery, in the LCCAs of the Nur77‑deficient mice, a significant increase in the intima-media area and carotid intima-media thickness was noted, as well as more severe elastin disruption and collagen deposition compared to the WT mice. Immunofluorescence staining revealed an increase in VSMC proliferation [determined by the expression of proliferating cell nuclear antigen (PCNA)] and matrix metalloproteinase 9 (MMP-9) production in the Nur77-deficient mice. There was no difference in the number of intimal apoptotic cells between the groups. Taken together, our results indicate that Nur77 may be a sensor of oxidative stress and an inhibitor of vascular remodeling induced by low shear stress. Nur77, as well as its downstream cell signals, may thus be a potential therapeutic target for the suppression of vascular remodeling.
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Copy and paste a formatted citation
Spandidos Publications style
Yu Y, Cai Z, Cui M, Nie P, Sun Z, Sun S, Chu S, Wang X, Hu L, Yi J, Yi J, et al: The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice. Int J Mol Med 36: 1547-1555, 2015.
APA
Yu, Y., Cai, Z., Cui, M., Nie, P., Sun, Z., Sun, S. ... He, B. (2015). The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice. International Journal of Molecular Medicine, 36, 1547-1555. https://doi.org/10.3892/ijmm.2015.2375
MLA
Yu, Y., Cai, Z., Cui, M., Nie, P., Sun, Z., Sun, S., Chu, S., Wang, X., Hu, L., Yi, J., Shen, L., He, B."The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice". International Journal of Molecular Medicine 36.6 (2015): 1547-1555.
Chicago
Yu, Y., Cai, Z., Cui, M., Nie, P., Sun, Z., Sun, S., Chu, S., Wang, X., Hu, L., Yi, J., Shen, L., He, B."The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice". International Journal of Molecular Medicine 36, no. 6 (2015): 1547-1555. https://doi.org/10.3892/ijmm.2015.2375
Copy and paste a formatted citation
x
Spandidos Publications style
Yu Y, Cai Z, Cui M, Nie P, Sun Z, Sun S, Chu S, Wang X, Hu L, Yi J, Yi J, et al: The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice. Int J Mol Med 36: 1547-1555, 2015.
APA
Yu, Y., Cai, Z., Cui, M., Nie, P., Sun, Z., Sun, S. ... He, B. (2015). The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice. International Journal of Molecular Medicine, 36, 1547-1555. https://doi.org/10.3892/ijmm.2015.2375
MLA
Yu, Y., Cai, Z., Cui, M., Nie, P., Sun, Z., Sun, S., Chu, S., Wang, X., Hu, L., Yi, J., Shen, L., He, B."The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice". International Journal of Molecular Medicine 36.6 (2015): 1547-1555.
Chicago
Yu, Y., Cai, Z., Cui, M., Nie, P., Sun, Z., Sun, S., Chu, S., Wang, X., Hu, L., Yi, J., Shen, L., He, B."The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice". International Journal of Molecular Medicine 36, no. 6 (2015): 1547-1555. https://doi.org/10.3892/ijmm.2015.2375
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