Raynaud's phenomenon (RP) is an episodic vasospasm of the peripheral arteries caused by an exaggerated reaction to cold temperature or emotional stress. Restoring the angiogenesis capability of the acral lesional skin is a critical strategy to treat RP. Local injection of botulinum toxin-A (BTX-A) has also been reported for treatment of RP. However, since the exact mechanisms of BTX-A action are still unclear, its administration for treatment of RP is not widely used. In the present study, BTX-A was found to promote angiogenesis and relieve RP in the patient. To elucidate its mechanisms against angiogenesis, BTX-A was used to treat human umbilical vein endothelial cells (HUVECs), one of the most popular in vitro models of angiogenesis, and RNA sequencing was used to investigate differentially expressed genes. A total of 413 genes were upregulated, and 1634 were downregulated, with fold-changes >2.0 in HUVECs treated with BTX-A. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed BTX-A affected expression of angiogenesis-associated, angiogenesis-associated signaling pathway-related, metabolic pathway, and epigenetic regulation-related genes. These results demonstrate potential biomarkers of BTX-A action, thereby providing potential therapeutic mechanism(s) by which BTX-A relieves RP symptoms.

中文翻译：

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BTX-A促进血管生成相关基因在人脐静脉内皮细胞中的表达

雷诺现象（RP）是由于对低温或情绪压力的过度反应引起的周围动脉的阵发性血管痉挛。恢复末端病变皮肤的血管生成能力是治疗RP的关键策略。也已经报道了局部注射肉毒杆菌毒素A（BTX-A）来治疗RP。但是，由于尚不清楚BTX-A作用的确切机制，因此其用于治疗RP的给药方法尚未广泛使用。在本研究中，发现BTX-A可以促进患者的血管生成并缓解RP。为了阐明其抗血管生成的机制，BTX-A被用于治疗人脐静脉内皮细胞（HUVEC），这是体外最受欢迎的一种血管生成模型，RNA测序用于研究差异表达基因。在用BTX-A处理的HUVEC中，总共413个基因被上调，而1634个基因被下调，其倍数变化> 2.0。基因本体注释和《京都基因与基因组百科全书》（KEGG）途径富集分析显示，BTX-A影响了与血管新生相关，与血管新生相关的信号通路相关，代谢途径和表观遗传调控相关基因的表达。这些结果证明了BTX-A作用的潜在生物标志物，从而提供了BTX-A缓解RP症状的潜在治疗机制。