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Article

Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia

  • Authors:
    • Mohammed M. Kassem
    • Furqan Muqri
    • Mary Dacosta
    • David Bruch
    • Vivian Gahtan
    • Kristopher G. Maier
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY 13210, USA, College of Medicine, MD Program, SUNY Upstate Medical University, Syracuse, NY 13210, USA
  • Pages: 1959-1964
    |
    Published online on: February 20, 2020
       https://doi.org/10.3892/mmr.2020.10994
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Abstract

Intimal hyperplasia (IH) is a pathologic process that leads to restenosis after treatment for peripheral arterial disease. Heat shock protein 90 (HSP90) is a molecular chaperone that regulates protein maturation. Activation of HSP90 results in increased cell migration and proliferation. 17‑N‑allylamino‑17‑demethoxygeldanamycin (17‑AAG) and 17‑dimethylaminoethylamino‑17‑demethoxygeldanamycin (17‑DMAG) are low toxicity Food and Drug Association approved HSP90 inhibitors. The current study hypothesized that HSP90 inhibition was predicted to reduce vascular smooth muscle cell (VSMC) migration and proliferation. In addition, localized HSP90 inhibition may inhibit post‑angioplasty IH formation. For proliferation, VSMCs were treated with serum‑free media (SFM), 17‑DMAG or 17‑AAG. The selected proliferative agents were SFM, platelet derived growth factor (PDGF) or fibronectin. After three days, proliferation was measured. For migration, VSMCs were treated with SFM, 17‑AAG or 17‑DMAG with SFM, PDGF or fibronectin as chemoattractants. Balloon injury to the carotid artery was performed in rats. The groups included in the present study were the control, saline control, 17‑DMAG in 20% pluronic gel delivered topically to the adventitia or intraluminal delivery of 17‑DMAG. After 14 days, arteries were fixed and sectioned for morphometric analysis. Data was analyzed using ANOVA or a student's t‑test. P<0.05 was considered to indicate a statistically significant difference. The results revealed that 17‑AAG and 17‑DMAG had no effect on cell viability. PDGF and fibronectin also increased VSMC proliferation and migration. Furthermore, both 17‑AAG and 17‑DMAG decreased cell migration and proliferation in all agonists. Topical adventitial treatment with 17‑DMAG after balloon arterial injury reduced IH. HSP90 inhibitors suppressed VSMC proliferation and migration without affecting cell viability. Topical treatment with a HSP90 inhibitor (DMAG) decreased IH formation after arterial injury. It was concluded that 17‑DMAG may be utilized as an effective therapy to prevent restenosis after revascularization.
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Copy and paste a formatted citation
Spandidos Publications style
Kassem MM, Muqri F, Dacosta M, Bruch D, Gahtan V and Maier KG: Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia. Mol Med Rep 21: 1959-1964, 2020.
APA
Kassem, M.M., Muqri, F., Dacosta, M., Bruch, D., Gahtan, V., & Maier, K.G. (2020). Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia. Molecular Medicine Reports, 21, 1959-1964. https://doi.org/10.3892/mmr.2020.10994
MLA
Kassem, M. M., Muqri, F., Dacosta, M., Bruch, D., Gahtan, V., Maier, K. G."Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia". Molecular Medicine Reports 21.4 (2020): 1959-1964.
Chicago
Kassem, M. M., Muqri, F., Dacosta, M., Bruch, D., Gahtan, V., Maier, K. G."Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia". Molecular Medicine Reports 21, no. 4 (2020): 1959-1964. https://doi.org/10.3892/mmr.2020.10994
Copy and paste a formatted citation
x
Spandidos Publications style
Kassem MM, Muqri F, Dacosta M, Bruch D, Gahtan V and Maier KG: Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia. Mol Med Rep 21: 1959-1964, 2020.
APA
Kassem, M.M., Muqri, F., Dacosta, M., Bruch, D., Gahtan, V., & Maier, K.G. (2020). Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia. Molecular Medicine Reports, 21, 1959-1964. https://doi.org/10.3892/mmr.2020.10994
MLA
Kassem, M. M., Muqri, F., Dacosta, M., Bruch, D., Gahtan, V., Maier, K. G."Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia". Molecular Medicine Reports 21.4 (2020): 1959-1964.
Chicago
Kassem, M. M., Muqri, F., Dacosta, M., Bruch, D., Gahtan, V., Maier, K. G."Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia". Molecular Medicine Reports 21, no. 4 (2020): 1959-1964. https://doi.org/10.3892/mmr.2020.10994
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