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Pachymic Acid Ameliorates Pulmonary Hypertension by Regulating Nrf2-Keap1-ARE Pathway

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Abstract

Objective

Pulmonary hypertension (PH) is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death. The purpose of this study was to investigate the mechanism by which pachymic acid (PA) pretreatment affects PH and pulmonary vascular remodeling in rats.

Methods

PH was induced via hypoxia exposure and administration of PA (5 mg/kg per day) in male Sprague-Dawley rats. Hemodynamic parameters were measured using a right ventricular floating catheter and pulmonary vascular morphometry was measured by hematoxylin-eosin (HE), α-SMA and Masson staining. MTT assays and EdU staining were used to detect cell proliferation, and apoptosis was analyzed by TUNEL staining. Western blotting and immunohistochemistry were used to detect the expression of proteins related to the Nrf2-Keap1-ARE pathway.

Results

PA significantly alleviated hypoxic PH and reversed right ventricular hypertrophy and pulmonary vascular remodeling. In addition, PA effectively inhibited proliferation and promoted apoptosis in hypoxia-induced pulmonary artery smooth muscle cells (PASMCs). Moreover, PA pretreatment inhibited the expression of peroxy-related factor (MDA) and promoted the expression of antioxidant-related factors (GSH-PX and SOD). Furthermore, hypoxia inhibited the Nrf2-Keap1-ARE signaling pathway, while PA effectively activated this pathway. Most importantly, addition of the Nrf2 inhibitor ML385 reversed the inhibitory effects of PA on ROS generation, proliferation, and apoptosis tolerance in hypoxia-induced PASMCs.

Conclusion

Our study suggests that PA may reverse PH by regulating the Nrf2-Keap1-ARE signaling pathway.

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Author notes

  1. The authors contributed equally to this work.

Authors and Affiliations

  1. Department of Ultrasound, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China

    Yuan He

  2. Department of Neurology, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China

    Jian-hua Zhong

  3. Department of Thoracic and Cardiovascular Surgery, Minda Hospital of Hubei Minzu University, Enshi, 445000, China

    Xiao-dong Wei

  4. Department of Pulmonary and Critical Care Medicine, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China

    Chu-ying Huang, Pai-lan Peng, Jun Yao, Xiu-sheng Song, Wan-li Fan & Guang-cai Li

Authors
  1. Yuan He
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  2. Jian-hua Zhong
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  3. Xiao-dong Wei
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  4. Chu-ying Huang
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  8. Wan-li Fan
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  9. Guang-cai Li
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Corresponding author

Correspondence to Guang-cai Li.

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The authors declare that they have no conflicts of interest concerning this article.

Additional information

This project was supported by the Natural Science Foundation of Hubei Province (No. 2017CFB769).

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He, Y., Zhong, Jh., Wei, Xd. et al. Pachymic Acid Ameliorates Pulmonary Hypertension by Regulating Nrf2-Keap1-ARE Pathway. CURR MED SCI 42, 56–67 (2022). https://doi.org/10.1007/s11596-021-2414-2

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  • DOI: https://doi.org/10.1007/s11596-021-2414-2

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