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The effect of Telmisartan on the expression of connexin43 and neointimal hyperplasia in a rabbit iliac artery restenosis model

  • Lu CaoEmail author
  • Cui Zhao
  • Hongliang Cong
  • Kai Hou
  • Lianghui Wan
  • Jixiang Wang
  • Lili Zhao
  • Haiyang Yan
Original Article
  • 32 Downloads

Abstract

We established a rabbit iliac artery restenosis model to explore the impact of Telmisartan on the expression of Connexin43 (Cx43) and neointimal hyperplasia. Thirty New Zealand white rabbits were randomly divided into three groups: control group (n = 10), restenosis group (n = 10), and Telmisartan group (n = 10). The restenosis model was established by high-cholesterol diet combined with double-balloon injury of iliac arteries. In addition, Telmisartan at 5 mg/(kg day) was administered to the rabbits of Telmisartan group on the second day after the second balloon injury. All rabbits were killed at the end of the experiment followed by institution policy. Before sacrifice, blood samples were obtained to test serum angiotensinII (AngII). Iliac arteries were isolated for morphological analysis and determining the expression of Cx43 by HE staining, immunohistochemical analysis, reverse transcription-polymerase chain reaction (RT-PCR), and Western Blotting analysis. Then, the local AngII levels of arteries were measured by radioimmunoassay. As compared with controls, the expression of Cx43 mRNA (0.98 ± 0.08) vs. (1.27 ± 0.17), P < 0.01), and Cx43 protein [(0.75 ± 0.08) vs. (0.90 ± 0.08), P < 0.05] of restenosis group were increased, which were significantly higher than those of Telmisartan group [Cx43 mRNA: (1.27 ± 0.17) vs. (1.00 ± 0.20), P < 0.01; Cx43 protein: (0.90 ± 0.08) vs. (0.82 ± 0.05), P < 0.05]. Furthermore, The intima thickness [(266.12 ± 70.27) vs. (2.85 ± 0.19) μm, P < 0.01] and the local AngII [(115.6 ± 15.7) vs. (90.1 ± 7.7), P < 0.05] of restenosis group were raised when compared with controls. Telmisartan group exhibited thinner intima compared with restenosis group [(68.22 ± 24.37) vs. (266.12 ± 70.27), P < 0.01]. However, the local AngII levels between these two groups were approximate. In addition, the plasma concentration of AngII was not significantly different among three groups. In conclusion, Telmisartan can inhibit the expression of connexin43 and neointimal hyperplasia in iliac artery restenosis model.

Keywords

Restenosis vascular smooth muscle cells Neointimal hyperplasia Angiotensin II Connexin43 Telmisartan 

Notes

Funding

The present study was supported by the Tianjin Municipal Health Bureau Science and Technology Foundation (no. 2010KZ61 and Grant no. 2013KR18).

Compliance with ethical standards

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

Conflict of Interest

The authors declare no potential conflict of interest.

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Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Lu Cao
    • 1
    Email author
  • Cui Zhao
    • 2
  • Hongliang Cong
    • 1
  • Kai Hou
    • 3
  • Lianghui Wan
    • 1
  • Jixiang Wang
    • 1
  • Lili Zhao
    • 1
  • Haiyang Yan
    • 4
  1. 1.Cardiology DepartmentTianjin Chest HospitalTianjinPeople’s Republic of China
  2. 2.National Center for Cardiovascular Diseases, Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPeople’s Republic of China
  3. 3.School of MedicineNankai UniversityTianjinPeople’s Republic of China
  4. 4.Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart CenterAffiliated Hospital of Logistics University of the Chinese People’s Armed Police ForcesTianjinPeople’s Republic of China

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