1. Academic Validation
  2. Cilostazol Promotes Angiogenesis and Increases Cell Proliferation After Myocardial Ischemia-Reperfusion Injury Through a cAMP-Dependent Mechanism

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

  • Cardiovasc Eng Technol. 2019 Dec;10(4):638-647. doi: 10.1007/s13239-019-00435-0.
Jiangjin Li 1 Xiaoli Xiang 2 Hai Xu 3 Yafei Shi 3
Affiliations

Affiliations

  • 1 Department of Cardiology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, Jiangsu, China. Lijiangjinlsl@163.com.
  • 2 Department of Nephrology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, Jiangsu, China.
  • 3 Department of Cardiology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, Jiangsu, China.
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

Angiogenesis; CAMP; Cilostazol; Ischemia–reperfusion injury; Myocardium.

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