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Involvement of CXCR4 and Stem Cells in a Rat Model of Pulmonary Arterial Hypertension

  • Tingting Zhang
  • Nanako Kawaguchi
  • Emiko Hayama
  • Yoshiyuki Furutani
  • Toshio NakanishiEmail author
Open Access
Conference paper
  • 535 Downloads

Abstract

Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome. C-X-C chemokine receptor type 4 (CXCR4) is known to be expressed in cancer and stem/progenitor cells. In the present study, PAH was induced in a rat model by 5 weeks of 10% hypoxia and treatment with a single subcutaneous injection of monocrotaline (60 mg/kg) [1] to investigate the involvement of CXCR4 in PAH development [2].

Keywords

Pulmonary arterial hypertension CXCR4 Mesenchymal stem cells Pulmonary vascular remodeling 

Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome. C-X-C chemokine receptor type 4 (CXCR4) is known to be expressed in cancer and stem/progenitor cells. In the present study, PAH was induced in a rat model by 5 weeks of 10% hypoxia and treatment with a single subcutaneous injection of monocrotaline (60 mg/kg) [1] to investigate the involvement of CXCR4 in PAH development [2].

The successful establishment of the PAH model was confirmed by significant differences in the right ventricular systolic pressure, Fulton index, wall thickness, vascular occlusion score determined by immunohistochemical staining, and the expression of inflammatory markers measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) between the PAH and control groups We compared the expression of CXCR4 and other stem cell markers in the PAH and control groups. The results of RT-qPCR revealed that the expression of CXCR4, SCF, c-Kit, and CD29 was significantly higher in the PAH group. Immunohistochemical staining also showed that the numbers of CXCR4-, c-Kit-, and CD90-positive cells were significantly higher in the PAH group. We hypothesized that these markers play important roles in chemotaxis, proliferation, and survival of smooth muscle cells or endothelial cells, leading to pulmonary vascular remodeling. Further studies to clarify the role of CXCR4 and stem cells in PAH development may provide additional treatment options, such as CXCR4 inhibitors.

Notes

Acknowledgment

The authors would like to acknowledge Mr. Kenji Yoshihara and Mr. Hiroaki Nagao at Tokyo Women’s Medical University for their excellent technical assistance.

References

  1. 1.
    Lan B, Hayama E, Kawaguchi N, et al. Therapeutic efficacy of valproic acid in a combined monocrotaline and chronic hypoxia rat model of severe pulmonary hypertension. PLoS One. 2015;10:e0117211.CrossRefGoogle Scholar
  2. 2.
    Zhang T, Kawaguchi N, Hayama E, et al. High expression of CXCR4 and stem cell markers in a monocrotaline and chronic hypoxia-induced rat model of pulmonary arterial hypertension. Exp Ther Med. 2018;15(6):4615–22.  https://doi.org/10.3892/etm.2018.6027.CrossRefPubMedPubMedCentralGoogle Scholar

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© The Author(s) 2020

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Authors and Affiliations

  • Tingting Zhang
    • 1
  • Nanako Kawaguchi
    • 1
  • Emiko Hayama
    • 1
  • Yoshiyuki Furutani
    • 1
  • Toshio Nakanishi
    • 1
    Email author
  1. 1.Department of Pediatric CardiologyTokyo Women’s Medical UniversityTokyoJapan

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