Single Intraosseous Injection of Simvastatin Promotes Endothelial Progenitor Cell Mobilization, Neovascularization, and Wound Healing in Diabetic Rats

Liu, Can; Zhu, Junxiong; Bai, Hai; Zhang, Wen; Wang, Hong; Leng, Huijie; Xu, Yan; Song, Chunli

doi:10.1097/prs.0000000000006502

Cited by 19 publications

(8 citation statements)

References 51 publications

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“…The major structural protein present in the dermal layer of the skin is collagen 66 . Liu et al also revealed that the collagen deposition was enhanced in the granulation tissue of the wounds treated with SIM 67 . The results obtained in the present research were in agreement with those of Asai et al 68 They reported that histologic wounds treated with SIM showed significantly higher degrees of the maturation of the granulation tissue, collagen deposition, and re‐epithelialization, in addition to neovascularization 68 …”

Section: Discussionsupporting

confidence: 89%

Comparing the wound healing effect of a controlled release wound dressing containing curcumin/ciprofloxacin and simvastatin/ciprofloxacin in a rat model: A preclinical study

Heydari

Kharazi

Asgary

et al. 2021

J Biomedical Materials Res

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Inflammation and infection are two main factors predisposing a wound to become a chronic one. Degradable wound dressings involving the controlled release of suitable drugs at the ulcer site are one of the solutions to make wounds healing progress smoothly and rapidly. In this research, biodegradable dressings made of polyglycerol sebacate/polycaprolactone (PGS/PCL) containing curcumin/ciprofloxacin (CUR/CIP) and simvastatin/ciprofloxacin (SIM/CIP) were prepared by using the coaxial electrospinning method. Transmission electron microscopy for uniform core/shell structure, swelling ratio, and drug release pattern of the wound dressings were evaluated. At the in vivo study, histometric, histopathologic, and collagen expression study was performed. The PGS/PCL samples containing SIM/CIP showed a burst release pattern of CIP with a delay in the release of SIM; meanwhile, in the samples containing CUR/CIP, both drugs showed a burst release behavior. No cytotoxicity response was observed in the study groups. The in vivo study showed that wound closure was almost completed only in the SIM/CIP group after 14 days. After 14 days, in the wound treated with SIM/CIP dressing, the amount of collagen deposition and angiogenesis was higher than that of the others. These results clearly showed the effect of SIM/CIP on the improvement of the wound healing efficiency in the long term (14 days) and the effect of CUR/CIP on wound contraction in the short term (4 day). It seems, therefore, that the use of SIM and CUR simultaneously in a wound dressing could cause a synergistic effect in the wound repair.

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Section: Discussionsupporting

confidence: 89%

Comparing the wound healing effect of a controlled release wound dressing containing curcumin/ciprofloxacin and simvastatin/ciprofloxacin in a rat model: A preclinical study

Heydari

Kharazi

Asgary

et al. 2021

J Biomedical Materials Res

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“…In addition, it received over-the-counter status in numerous countries. Our previous results showed that local i.o.-injected simvastatin increased the mobilization of EPCs and osteogenic bone marrow-derived mesenchymal stem cells to peripheral blood [ 14 , 35 ], promoted peripheral nerve regeneration [ 36 ], and enhanced bone formation and angiogenesis [ 15 , 29 ]. In this study, we demonstrated that local i.o.-injected simvastatin suppressed the growth of breast cancer, while none of p.o., i.v., s.c. or i.p.…”

Section: Discussionmentioning

confidence: 99%

Single-dose local intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization

Yuan

Bai

Ren

et al. 2020

Translational Oncology

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Tumor vessels play important roles in cancer development and angiogenesis has been characterized as an essential process for tumor cell tumor growth. Our previous studies found that a single-dose local intraosseous simvastatin injection rapidly and long-termly mobilized bone marrow-derived endothelial progenitor cells to peripheral blood, promoting angiogenesis and ameliorating ischemia injury. However, whether intraosseous injection of simvastatin participates in cancer progression and the role of angiogenesis enhancement in this process remain unknown. In this study, we found that intraosseous injection of simvastatin improves tumor vascular structure, along with increasing the percentage of pericyte coverage on tumor vessels, and reducing vascular permeability, tumor hypoxia and tumor necrosis. Further, we demonstrate that a single-dose local intraosseous simvastatin injection suppresses tumor growth, facilitates sensitivity of chemotherapy and prolongs survival in breast cancer-bearing mice. In addition, oral application, intravenous, subcutaneous and intraperitoneal injection of simvastatin do not show these effects. Taken together, these results demonstrate that intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization, which might be a promising strategy for cancer treatment.

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“…Intraocular neovascularization is a common pathological feature of various ischemic retinopathy [15,16]. Although the occurrence of neovascularization is a protective response of the body, which plays an important role in tissue repair and ischemia-reperfusion [17,18], its secondary lesions such as intraocular hemorrhage, retinal proliferation, traction retinal detachment and neovascular glaucoma can lead to loss of vision [19,20]. In order to control intraocular neovascularization more effectively, Clinically, antiangiogenic drugs have become a powerful weapon in the treatment of neovascularization, especially choroidal neovascularization, the researchers even taken a variety of combined treatment, such as anti-VEGF drugs combined with photodynamic therapy, anti-VEGF drugs combined with glucocorticoid therapy, but the recurrent neovascularization problem can not be solved effectively.…”

Section: Discussionmentioning

confidence: 99%

P53/DRAM/ autophagy - a new target for improving the therapeutic effect of anti-VEGF on intraocular neovascularization

Wang

Yao²,

et al. 2020

Preprint

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Backgroud Recurrence of intraocular neovascularization is a major clinical problem. Anti-VEGF drugs are the main treatment for intraocular neovascularization currently. However, anti-VEGF drugs can activate endothelial autophagy and weaken the therapeutic effect. This study aims to elucidate the effect and mechanism of anti-VEGF drugs on autophagy of vascular endothelial cells. Methods RF/6A cells were randomly divided into five groups: The control group, hypoxia group (1% O2、5% CO2、94% N2), anti-VEGF group(group1:Ranibizumab 100ug/ml; group2: Aflibercept, 400ug/ml; group3: Conbercept, 100ug/ml) and autophagy inhibition group(3-MA or CQ) which was corresponding to anti-VEGF group. Autophagy-related proteins were examined by Western blot. RFP-GFP-LC3 was used to detect autophagy and autophagic flow. CCK-8 assay was used to detect cell proliferation. Flow cytometry and Tunel was used to detect cell apoptosis. Cell migration and tube formation were assessed by wound assay and matrix method, respectively. Results Ranibizumab and Conbercept can triger autophagy in hypoxia condition in RF/6A cells, while Aflibercept can inhibit autophagy. Conbercept combined with autophagy inhibitor (3-MA or CQ) could inhibit cell migration and tube formation of RF/6A cells more effectively in hypoxia condition. For mechanism, p53 and DRAM proteins paly an important role in Conbercept induced autophagy. Inhibition of P53 can suppressed the autophagy induced by Conbercept. Conclusion Ranibizumab and Conbercept can triger the autophagy of vascular endothelial cells while Aflibercept can inhibit it. The combination of ranibizumab/ Concept and autophagy inhibitor can significantly inhibit the formation of angiogenesis in vitro. The mechanism of autophagy activation is related to the activation of p53 / DRAM pathway.

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Single Intraosseous Injection of Simvastatin Promotes Endothelial Progenitor Cell Mobilization, Neovascularization, and Wound Healing in Diabetic Rats

Cited by 19 publications

References 51 publications

Comparing the wound healing effect of a controlled release wound dressing containing curcumin/ciprofloxacin and simvastatin/ciprofloxacin in a rat model: A preclinical study

Comparing the wound healing effect of a controlled release wound dressing containing curcumin/ciprofloxacin and simvastatin/ciprofloxacin in a rat model: A preclinical study

Single-dose local intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization

P53/DRAM/ autophagy - a new target for improving the therapeutic effect of anti-VEGF on intraocular neovascularization

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