The Effect of Atorvastatin on the Viability of Ischemic Skin Flaps in Diabetic Rats

Jia, Yuechen; Xu, Jia; Chen, Honghao; Kang, Qinglin; Chai, Yimin

doi:10.1097/prs.0000000000002984

Cited by 5 publications

(5 citation statements)

References 31 publications

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“…Multiple studies describe various approaches for enhancing skin flap survival, ranging from gene delivery, 17 stem cell-based therapies, 18 and drug repurposing. 19 Still, an effective and widely accepted method ensuring skin flap survival has not emerged. This leaves patients with an underlying susceptibility to develop flap failure.…”

Section: Clinical Problem Addressedmentioning

confidence: 99%

Enhanced Survival and Accelerated Perfusion of Skin Flap to Recipient Site Following Administration of Human α1-Antitrypsin in Murine Models

Schuster

Bar-Nathan

Tiosano

et al. 2019

Advances in Wound Care

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Objective: Skin flaps are routinely used in reconstructive surgery yet remain susceptible to ischemia and necrosis. Distant flaps require lengthy time to detach causing patient discomfort. Human a1-antitrypsin (hAAT) is a clinically available serum glycoprotein. hAAT was shown to support mature vessel formation and enhance tissue survival following ischemia-reperfusion injuries. The purpose of the presented study was to examine the effect of hAAT on skin flap survival and distant ''tube'' flap perfusion through its recipient site. Approach: Random-pattern skin flaps were performed on mice treated with clinical-grade hAAT using three unique routes of administration (transgenic, i.p. and s.c. infiltration); necrotic area and tissue perfusion were assessed. Blockade of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS) were used to explore aspects of mechanism of action. A distant tube flap model was performed to examine time to perfusion. Results: hAAT-treated mice displayed approximately two-fold smaller necrotic flap areas versus controls across all hAAT administration routes. Flaps displayed greater perfusion as early as 3 days postsurgery (64.6% -4.0% vs. 43.7% -1.7% in controls; p = 0.007). hAAT-mediated flap survival was prominently NOS dependent, but only partially VEGF dependent. Finally, distant flaps treated with hAAT displayed significantly earlier perfusion versus controls (mean 9.6 -1.6 vs. 13.1 -1.0 days; p = 0.0005). Innovation: The established safety record of hAAT renders it an attractive candidate toward improving skin flap surgery outcomes, particularly during VEGF blockade. Conclusions: hAAT treatment enhances survival and accelerates perfusion of skin flaps in animal models in a NOS-dependent manner, partially circumventing VEGF blockade. Further mechanistic studies are required.

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Section: Clinical Problem Addressedmentioning

confidence: 99%

Enhanced Survival and Accelerated Perfusion of Skin Flap to Recipient Site Following Administration of Human α1-Antitrypsin in Murine Models

Schuster

Bar-Nathan

Tiosano

et al. 2019

Advances in Wound Care

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“…Activation of the SDF-1α/C-X-C chemokine receptor 4 (CXCR4) axis has been implicated in the process of angiogenesis, including recruitment of endothelial progenitor cells (EPCs) [23,24] and endothelial cell migration [25]. EPCs are a type of bone marrow-derived premature progenitor cells [26], which are characterized as CD45 low /CD34 + /VEGFR2 + [27]. Accumulating evidence has indicated that glucocorticoid abuse reduces the quantity and quality of circulating EPCs [28], which play a significant role in vascular repair in the ischemic necrotic area of SONFH [29].…”

Section: Introductionmentioning

confidence: 99%

Silencing MicroRNA-137-3p, which Targets RUNX2 and CXCL12 Prevents Steroid-induced Osteonecrosis of the Femoral Head by Facilitating Osteogenesis and Angiogenesis

Kong¹,

Zuo²,

Wang³

et al. 2020

Int. J. Biol. Sci.

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The main pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH) includes decreased osteogenic capacity of bone marrow-derived mesenchymal stem cells (BMSCs) and damaged blood supply to the femoral head. MicroRNAs (miRNAs) have been shown to play prominent roles in SONFH development. However, there is no report that a specific miRNA targeting two genes in two different pathogenic pathways has been applied to this disease. The present study investigated the effects of transplantation of miR-137-3p-silenced BMSCs on the prevention and early treatment of SONFH. First, western blotting and dual luciferase assays were employed to verify that miR-137-3p directly targets Runx2 and CXCL12. Then, silencing of miR-137-3p was found to facilitate osteogenic differentiation of BMSCs, which was confirmed by alkaline phosphatase (ALP) staining, alizarin red staining and qRT-PCR. Silencing of miR-137-3p also promoted angiogenesis by human umbilical vein endothelial cells (HUVECs) in the presence or absence of glucocorticoids. Thereafter, overexpression of Runx2 and CXCL12 without the 3′ untranslated region (3′UTR) partially rescued the effects of miR-137-3p on osteogenesis and angiogenesis, respectively. This finding further supported the hypothesis that miR-137-3p exerts its functions partly by regulating the genes, Runx2 and CXCL12. We also demonstrated that SONFH was partially prevented by transplantation of miR-137-3p-silenced BMSCs into a rat model. Micro-CT and histology showed that the transplantation of miR-137-3p-silenced BMSCs significantly improved bone regeneration. Additionally, the results of enzyme-linked immunosorbent assays (ELISA) and flow cytometry suggested that stromal cell-derived factor-1α (SDF-1α) and endothelial progenitor cells (EPCs) participated in the process of vascular repair. Taken together, these findings show that silencing of miR-137-3p directly targets the genes, Runx2 and CXCL12, which can play critical roles in SONFH repair by facilitating osteogenic differentiation and mobilizing EPCs.Key words: steroid-induced osteonecrosis of the femoral head, miR-137-3p, bone marrow-derived mesenchymal stem cells, CXCL12 (SDF-1α), Runx2, endothelial progenitor cells

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“…[6][7][8][9][10][11][12] The evaluation of the results of interventions performed in experimental models of skin grafts and flaps include some methods, such as gene expression analysis, 10,13 protein expression analysis, 11,12,[14][15][16] assessment of histological changes, 11,12,15 and the percentage of viable tissue. 6,7,17,18 The latter is widely used for being fast, inexpensive, and efficient. Three methods can be used to evaluate the percentage of viable tissue: weight of paper template (WPT), 17,18 paper template area (PTA), 19 and photographic area (PA).…”

Section: Introductionmentioning

confidence: 99%

A Comparison of Three Methods for the Analysis of Skin Flap Viability: Reliability and Validity

Tim

Martignago

Silva

et al. 2018

Advances in Wound Care

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Technological advances have provided new alternatives to the analysis of skin flap viability in animal models; however, the interrater validity and reliability of these techniques have yet to be analyzed. The present study aimed to evaluate the interrater validity and reliability of three different methods: weight of paper template (WPT), paper template area (PTA), and photographic analysis. Sixteen male Wistar rats had their cranially based dorsal skin flap elevated. On the seventh postoperative day, the viable tissue area and the necrotic area of the skin flap were recorded using the paper template method and photo image. The evaluation of the percentage of viable tissue was performed using three methods, simultaneously and independently by two raters. The analysis of interrater reliability and viability was performed using the intraclass correlation coefficient and Bland Altman Plot Analysis was used to visualize the presence or absence of systematic bias in the evaluations of data validity. The results showed that interrater reliability for WPT, measurement of PTA, and photographic analysis were 0.995, 0.990, and 0.982, respectively. For data validity, a correlation >0.90 was observed for all comparisons made between the three methods. In addition, Bland Altman Plot Analysis showed agreement between the comparisons of the methods and the presence of systematic bias was not observed. Digital methods are an excellent choice for assessing skin flap viability; moreover, they make data use and storage easier. Independently from the method used, the interrater reliability and validity proved to be excellent for the analysis of skin flaps' viability.

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The Effect of Atorvastatin on the Viability of Ischemic Skin Flaps in Diabetic Rats

Abstract: Atorvastatin notably promoted neovascularization and enhanced the viability of ischemic skin flaps in diabetic rats, which may be mediated at least partially by augmenting the number and restoring the functional capacity of endothelial progenitor cells.

Cited by 5 publications

References 31 publications

Enhanced Survival and Accelerated Perfusion of Skin Flap to Recipient Site Following Administration of Human α1-Antitrypsin in Murine Models

Enhanced Survival and Accelerated Perfusion of Skin Flap to Recipient Site Following Administration of Human α1-Antitrypsin in Murine Models

Silencing MicroRNA-137-3p, which Targets RUNX2 and CXCL12 Prevents Steroid-induced Osteonecrosis of the Femoral Head by Facilitating Osteogenesis and Angiogenesis

A Comparison of Three Methods for the Analysis of Skin Flap Viability: Reliability and Validity

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