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复发马蹄内翻足挛缩侧微血管和小动脉密度增加。

Increased Microvessel and Arteriole Density in the Contracted Side of the Relapsed Clubfoot.

机构信息

Department of Orthopaedics, Masaryk Hospital.

Faculty of Health Studies, Jan Evangelista Purkyne University, Usti nad Labem.

出版信息

J Pediatr Orthop. 2020 Nov/Dec;40(10):592-596. doi: 10.1097/BPO.0000000000001563.

DOI:10.1097/BPO.0000000000001563
PMID:32379245
Abstract

BACKGROUND

Clubfoot deformity (pes equinovarus) is one of the most common birth defects, and its etiology is still unknown. Initial clubfoot treatment is based on the Ponseti method throughout most of the world. Despite the effectiveness of this therapy, clubfoot may relapse. Recent studies confirm the theory of active fibrotic remodeling processes in the extracellular matrix of the affected tissue. The aim of this study was to clarify whether relapses in clubfoot therapy are associated with altered angiogenesis and to suggest possible regulatory pathways of this pathologic process.

METHODS

We compared microvessel density, arteriole density, and concentration of angioproliferative-related proteins found between tissues in the contracted, that is, the medial side (M-side), and noncontracted, that is, the lateral side (L-side) of the relapsed clubfeet. Tissue samples from 10 patients were analyzed. Histopathologic analysis consisted of immunohistochemistry and image analysis. Real-time polymerase chain reaction was used to study mRNA expression.

RESULTS

An increase in microvessel and arteriole density was noted in contracted, relapsed clubfoot tissue. This was accompanied by a significant increase in the levels of the vascular endothelial growth factor, vascular endothelial growth factor receptor 2, β catenin and active β catenin. Vascular endothelial growth factor, vascular endothelial growth factor receptor 2, and CD31 overexpression was also seen with mRNA analysis.

CONCLUSIONS

Increased microvessel and arteriole density in the contracted side of the relapsed clubfoot was noted. These processes are mediated by specific proangiogenic proteins that are overexpressed in the contracted tissue. These findings contribute to the etiology and the development of relapses in the treatment of clubfoot.

LEVEL OF EVIDENCE

Level II-analytical and prospective.

摘要

背景

马蹄足畸形(足内翻)是最常见的出生缺陷之一,其病因尚不清楚。最初的马蹄足治疗方法是在世界范围内基于 Ponseti 方法。尽管这种疗法有效,但马蹄足可能会复发。最近的研究证实了受影响组织细胞外基质中活跃的纤维性重塑过程的理论。本研究旨在阐明马蹄足治疗的复发是否与血管生成的改变有关,并提出该病理过程的可能调节途径。

方法

我们比较了挛缩(即内侧(M 侧))和非挛缩(即外侧(L 侧))复发马蹄足组织中微血管密度、小动脉密度和血管增殖相关蛋白浓度。分析了 10 名患者的组织样本。组织病理学分析包括免疫组织化学和图像分析。实时聚合酶链反应用于研究 mRNA 表达。

结果

在挛缩的复发马蹄足组织中观察到微血管和小动脉密度增加。这伴随着血管内皮生长因子、血管内皮生长因子受体 2、β连环蛋白和活性β连环蛋白水平的显著增加。血管内皮生长因子、血管内皮生长因子受体 2 和 CD31 的 mRNA 分析也显示过表达。

结论

在复发的马蹄足的挛缩侧注意到微血管和小动脉密度增加。这些过程是由特定的促血管生成蛋白介导的,这些蛋白在挛缩组织中过度表达。这些发现有助于解释马蹄足治疗复发的病因和发展。

证据水平

II 级分析和前瞻性。

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引用本文的文献

1
The possible role of hypoxia in the affected tissue of relapsed clubfoot.缺氧在复发性马蹄内翻足受累组织中的可能作用。
Sci Rep. 2022 Mar 15;12(1):4462. doi: 10.1038/s41598-022-08519-z.
2
Increased Collagen Crosslinking in Stiff Clubfoot Tissue: Implications for the Improvement of Therapeutic Strategies.僵硬性马蹄内翻足组织中胶原交联增加:对改善治疗策略的影响。
Int J Mol Sci. 2021 Nov 2;22(21):11903. doi: 10.3390/ijms222111903.