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Cilostazol protects vessels against hyperglycemic injury and accelerates healing after implantation of drug-eluting stent in a type 1 diabetes mellitus rat aorta stent model

      Highlights

      • We investigated whether cilostazol was effective in a DES in a type I DM rat model.
      • Four weeks later, cilostazol decreased the expressions of VCAM and ICAM in aortic wall.
      • Cilostazol decreased the apoptotic cell ratio of the media.
      • In the modified aortic ring test, cilostazol preserved angiogenic potential of aorta.
      • Cilostazol enhanced re-endothelialization by von Willebrand factor expression.

      Abstract

      Objective

      Cilostazol, a selective phosphodiesterase-3 (PDE-3) inhibitor, can effectively suppress platelet activation and attenuate the increase in carotid intima-media thickness in diabetes mellitus (DM) patients. Therefore, we investigated whether cilostazol had effects on the healing process after implantation of a drug-eluting stent (DES) in a rat model of type 1 DM.

      Methods and results

      Streptozotocin-induced DM rats were divided into 2 groups in which cilostazol (30 mg/kg/day; DM-Cilostazol) or vehicle (DM-Vehicle) was orally administered. Age-matched rats treated with the vehicle were used as a control group (NDM-Vehicle). After 4 weeks, cilostazol changed the expression of vascular cell adhesion molecule and intercellular adhesion molecule and the apoptotic cell ratio of the media (DM-Vehicle: 53.5 ± 9.8%, DM-Cilostazol: 26.4 ± 8.3%, p < 0.05) in the aortic wall. Also, in a modified aortic ring test, cilostazol preserved the angiogenic potential of the aorta ([height of the sprouting tubes] DM-Vehicle: 0 ± 0 μm, DM-Cilostazol: 344.6 ± 236.8 μm, p < 0.05). After implantation of paclitaxel-eluting stents (PES) in rats treated with cilostazol or vehicle, thrombus formation, deposition of fibrin, and infiltration of inflammatory cells were attenuated by cilostazol. In particular, the re-endothelialization by von Willebrand factor expression in the DM-PES-Cilostazol group was enhanced compared with that in the DM-PES-Vehicle group.

      Conclusion

      Cilostazol has potential for protecting vessels against hyperglycemic injury and for accelerating the healing process after implantation of DES.

      Keywords

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