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Cardiovascular Engineering and Technology

, Volume 10, Issue 4, pp 638–647 | Cite as

Cilostazol Promotes Angiogenesis and Increases Cell Proliferation After Myocardial Ischemia–Reperfusion Injury Through a cAMP-Dependent Mechanism

  • Jiangjin LiEmail author
  • Xiaoli Xiang
  • Hai Xu
  • Yafei Shi
Original Article
  • 92 Downloads

Abstract

Purpose

Previous study indicated the protective role of cilostazol in ischemia–reperfusion (I/R) injury. Here, we aimed to explore the function of cilostazol in myocardial I/R injury and the underlying mechanism.

Methods

The myocardial I/R injury rat model was constructed, and the expression levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor receptor b (PDGF-B) and the number of new blood vessels were measured by qRT-PCR and immunohistochemistry. VSMC and HUVEC cells were treated with hypoxia to induce in vivo I/R injury model. The protein expression of AKT, endothelial nitric oxide synthase (eNOS) and apoptosis-related protein levels were detected by western blotting. Besides, the positive staining rate and cell viability were tested by 5-bromo-2-deoxyuridine (Brdu)/4′,6-diamidino-2-phenylindole (DAPI) or DAPI/TdT-mediated dUTP Nick-End Labeling (TUNEL) staining and MTT assay.

Results

Cilostazol promoted angiogenesis by increasing the number of new blood vessels and up-regulating the expression of VEGF, HGF, bFGF and PDGF-B in myocardial I/R-injury rat model. The in vitro experiments showed that cilostazol increased the level of eNOS and AKT, and also enhanced cell proliferation in hypoxia-treated VSMC and HUVEC cells. Furthermore, after 8-Br-cAMP treatment, VEGF, HGF, bFGF, PDGF-B, p-AKT and p-eNOS expression were up-regulated, while cleaved-caspase 3 and cleaved-PARP expression were down-regulated. In addition, the effects of cilostazol on cell viability and apoptosis were aggravated by 8-Br-cAMP and attenuated after KT-5720 treatment.

Conclusion

Cilostazol could promote angiogenesis, increase cell viability and inhibit cell apoptosis, consequently protecting myocardial tissues against I/R-injury through activating cAMP.

Keywords

Cilostazol Ischemia–reperfusion injury Myocardium CAMP Angiogenesis 

Notes

Competing interests

The authors declare that they have no competing interests, and all authors should confirm its accuracy.

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Copyright information

© Biomedical Engineering Society 2019

Authors and Affiliations

  1. 1.Department of CardiologyThe Affiliated Huaian No.1 People’s Hospital of Nanjing Medical UniversityHuai’anChina
  2. 2.Department of NephrologyThe Affiliated Huaian No.1 People’s Hospital of Nanjing Medical UniversityHuai’anChina

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