Cilostazol improves high glucose-induced impaired angiogenesis in human endothelial progenitor cells and vascular endothelial cells as well as enhances vasculoangiogenesis in hyperglycemic mice mediated by the adenosine monophosphate-activated protein kinase pathway

Tseng, Shuo Yen; Chao, Ting‐Hsing; Li, Yi Heng; Liu, Ping Yen; Lee, Cheng‐Han; Cho, Chung Lung; Wu, Hua; Chen, Jyh Hong

doi:10.1016/j.jvs.2014.10.103

Cited by 22 publications

(54 citation statements)

References 37 publications

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“…Therefore, the protective eff ect of cilostazol on oxidative stress and systemic cytokines release, which has been described in other studies, could benefi t such patients [31]. Finally, experimental data have shown that cilostazol seems to promote angiogenesis in both endothelial progenitor cells and vascular endothelial cells as well [32].…”

Section: At 28 Daysmentioning

confidence: 77%

Conservative treatment of patients with thromboangiitis obliterans or cannabis-associated arteritis presenting with critical lower limb ischaemia

Galyfos

Kerasidis

Kastrisios

et al. 2017

Vasa

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Summary: Background:Proper management of patients with thromboangiitis obliterans (TAO) or cannabis-associated arteritis (CAA), presenting with critical lower limb ischaemia (CLI) remains controversial, and data are limited. Patients and methods: Patients with TAO or CAA presenting with CLI between 2011 and 2016 were retrospectively evaluated. Patients requiring primary intervention were excluded. Conservative treatment included: (a) weight-adjusted bemiparin plus six hours/day intravenous iloprost for 28 days, (b) aspirin (100 mg/day) plus cilostazol (100 mg twice/day) after discharge, and (c) strict recommendations/monitoring for smoking cessation. Main outcomes included symptom recession, ankle-brachial index (ABI) improvement, and healing of lesions at the time of discharge as well as amputation, revascularization, and abstinence rate during follow-up. Results: Overall, 23 patients (TAO: 15; CAA: 8) were included within six years, none of the patients reported any other factor than smoking. All patients presented with rest pain and 12 patients with ulcer or necrotic lesions. Mean ABI measurement at presentation was 0.46 ± 0.2, after 28 days of treatment, all patients showed improvement regarding clinical picture and ABI measurement (0.54 ± 0.1; p < 0.05). During follow-up, only three patients underwent bypass surgery and two patients underwent major amputation, although the smoking abstinence rate was very low (13 %). Conclusions: Intravenous iloprost plus bemiparin for 28 days together with per os aspirin plus cilostazol seem to produce promising results in patients with TAO/CAA, treated for CLI, even with a low smoking abstinence rate. However, larger series are needed to further evaluate inter-group differences and potential prognostic factors.

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Section: At 28 Daysmentioning

confidence: 77%

Conservative treatment of patients with thromboangiitis obliterans or cannabis-associated arteritis presenting with critical lower limb ischaemia

Galyfos

Kerasidis

Kastrisios

et al. 2017

Vasa

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“…However whether cilostazol could be used as a potential drug to target DCs warrants further study. Some reports have shown that the effect of cilostazol is associated with the activation of the AMPK pathway, and this effect has been validated in various models [20,21,24,25]. Furthermore, AMPK has been suggested to play an important role in TLRs-induced IL-23 production [26].…”

Section: Discussionmentioning

confidence: 91%

“…3, IL23A promoter activity was * P < 0.05 vs. zymosan alone, ** P < 0.01 vs. zymosan alone, # P < 0.05 vs. cilostazol plus zymosan treatment. [20,21]. Thus, we aimed to clarify whether the inhibitory effect of cilostazol on IL-23 production by mo-DCs was mediated by AMPK by treating cells with an AMPK agonist (A-769662) and an AMPK antagonist (Compound C).…”

Section: Cilostazol Inhibited Myd88-induced Il23a Transcriptional Actmentioning

confidence: 99%

Cilostazol Suppresses IL-23 Production in Human Dendritic Cells via an AMPK-Dependent Pathway

Shi¹,

Yin²,

Liu³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Cilostazol has been previously demonstrated to inhibit IL-23 production in human synovial macrophages via a RhoA/ROCK-dependent pathway. However, whether cilostazol affects IL-23 production in human dendritic cells remains largely unknown. The present study was designed to investigate this question and elucidate the possible underlying mechanisms. Methods: Human monocyte-derived dendritic cells (mo-DCs) were pretreated with or without cilostazol and then incubated with zymosan. Enzyme-linked immunosorbent assay (ELISA) and real time PCR analyses were used to measure IL-23 protein expression and RNA levels, respectively, whereas Western blotting was used to measure the expression and phosphorylation level of AMPK. Results: Our results demonstrated that cilostazol suppressed zymosan-induced IL-23 protein production in a concentration dependent manner without affecting dendritic cell viability. In addition, it was found that cilostazol suppressed the expression of the p19 and p40 subunits of IL-23. Moreover, cilostazol mimicked the effect of the AMPK agonist A-769662, as demonstrated by the fact that IL-23 production was also inhibited by A-769662, and the effect of cilostazol on IL-23 production was blocked by the AMPK antagonist Compound C. More importantly, Western blotting demonstrated that cilostazol led to an increased phosphorylation of AMPK. Conclusion: Collectively, our data suggest that cilostazol inhibits the production of IL-23 in human mo-DCs, potentially via the activation of AMPK. This suggests that cilostazol could be an effective anti-inflammatory agent in IL-23- and dendritic cell-related diseases.

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“…Cilostazol, a selective phosphodiesterase 3 inhibitor, is a commercially available drug that provides antiplatelet and vasodilatory effects mediated by an increase in intracellular cyclic adenosine monophosphate levels [4, 12, 13] and is prescribed to patients with peripheral artery disease only with intermittent claudication. However, there is still a lack of evidence supporting the benefits of this compound in CLI.…”

Section: Introductionmentioning

confidence: 99%

“…However, there is still a lack of evidence supporting the benefits of this compound in CLI. Notably, cilostazol could provide additional cellular and proangiogenic effects, including protection of ECs from apoptosis [4, 12, 14], stimulation of the release of angiogenic factors [4, 15], and improved endothelial function of ECs [4, 12], thereby potentially enhancing angiogenesis [4, 12, 16]. However, the effects of cilostazol on the functions of human early EPCs and its potential mechanisms related to SDF-1 α /CXCR4 pathway are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Cilostazol Improves Proangiogenesis Functions in Human Early Endothelial Progenitor Cells through the Stromal Cell-Derived Factor System and Hybrid Therapy Provides a Synergistic EffectIn Vivo

Tseng

Chao

et al. 2016

BioMed Research International

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This study investigated the effect of cilostazol on proangiogenesis functions in human early endothelial progenitor cells (EPCs) in vitro and the therapeutic implication of hybrid therapy with cilostazol and human early EPCs in vivo. Cilostazol significantly increased colony-forming units and enhanced differentiation of EPCs toward endothelial lineage. Treatments resulted in antiapoptotic effects and stimulated proliferation and migration and in vitro vascular tube formation through activation of stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)/phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway. Blood flow recovery and capillary density in murine ischemic hindlimbs were significantly improved in cilostazol-treated, human early EPCs-treated, and cotreatment groups. The effects were attenuated with SDF-1α inhibition. Plasma SDF-1α levels were significantly higher in 3 active treatment groups after surgery, with greatest effects observed in hybrid therapy. The angiogenic effects of transplanted EPCs pretreated with cilostazol ex vivo were superior to untreated EPCs using in vivo Matrigel assay. Implanted EPCs were incorporated into the capillary, with pretreatment or cotreatment with cilostazol resulting in enhanced effects. Taken together, cilostazol promotes a large number of proangiogenic functions in human early EPCs through activation of SDF-1/CXCR4/PI3K/Akt signaling, and hybrid therapy provides a synergistic effect in vivo. Cotreatment may be beneficial in ischemic disease.

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Cilostazol improves high glucose-induced impaired angiogenesis in human endothelial progenitor cells and vascular endothelial cells as well as enhances vasculoangiogenesis in hyperglycemic mice mediated by the adenosine monophosphate-activated protein kinase pathway

Abstract: Cilostazol prevents HG-induced endothelial dysfunction in EPCs and HUVECs and enhances angiogenesis in hyperglycemic mice by interactions with a broad signaling network, including activation of AMPK/ACC and probably cAMP/PKA pathways.

Cited by 22 publications

References 37 publications

Conservative treatment of patients with thromboangiitis obliterans or cannabis-associated arteritis presenting with critical lower limb ischaemia

Conservative treatment of patients with thromboangiitis obliterans or cannabis-associated arteritis presenting with critical lower limb ischaemia

Cilostazol Suppresses IL-23 Production in Human Dendritic Cells via an AMPK-Dependent Pathway

Cilostazol Improves Proangiogenesis Functions in Human Early Endothelial Progenitor Cells through the Stromal Cell-Derived Factor System and Hybrid Therapy Provides a Synergistic EffectIn Vivo

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