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Radiation suppresses neointimal hyperplasia through affecting proliferation and apoptosis of vascular smooth muscle cells

Abstract

Purpose

To study the effect of x-ray radiotherapy on vascular smooth muscle cells (VSMCs) and elucidate the mechanisms in preventing neointimal hyperplasia of prosthetic vascular grafts.

Materials and methods

In model I, twelve mongrel dogs underwent revascularization with prosthetic grafts and half the dogs underwent irradiation of the grafts at 28 Gy. In model II, human VSMCs (hVSMCs) were maintained and divided into six groups to which external radiation was applied at six different doses: 0 Gy, 2 Gy, 8 Gy, 16 Gy, 24 Gy and 30 Gy. In both models, specimens were harvested and examined by using morphological, immunological, cellular and molecular methods.

Results

After irradiation, the neointima thickness was significantly lower in irradiated groups (p≤0.01). The radiotherapy could up-regulate p27kip1, and down-regulate proliferating cell nuclear antigen (PCNA) and S phase kinase associated protein 2 (Skp2). X-ray irradiation inhibits the proliferation of hVSMCs via acting on G1/S phase of cell cycle. The apoptosis of hVSMCs increased significantly with dose and time. The expression of PCNA and Skp2 were decreased after a first increasing trend with dose, but had a significant negative correlation with time. The expression of p27kip1 had a significant positive correlation with dose and time.

Conclusions

Postoperative external fractionated irradiation after prosthetic vessel replacement of the abdominal aorta suppressed the development of hyperplasia in the graft neointima in the short term. There was a prominent time- and dose-dependent inhibition of VSMC proliferation by radiation when it was administered.

Post author correction

Article Type: ORIGINAL RESEARCH ARTICLE

Article Subject: Interventional radiology

DOI:10.5301/jva.5000804

Authors

Liqin Yuan, Chang Shu, Xiao Zhou, Jiehua Li, Lunchang Wang, Xin Li, Xiang Xiong, Lun Li

Article History

Disclosures

Financial support: National Natural Science Foundation of China (81370430).
Conflict of interest: None of the authors has financial interest related to this study to disclose.

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Authors

Affiliations

  • Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan - China
  • Department of Vascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan - China
  • Department of Head and Neck Surgery, The affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan - China

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