关键词: angiogenesis endothelial cells endothelial dysfunction erucin hyperglicemia isothiocyanate

Mesh : Humans Human Umbilical Vein Endothelial Cells / drug effects Glucose Vascular Endothelial Growth Factor A / metabolism Isothiocyanates / pharmacology Cell Movement / drug effects Paxillin / metabolism Angiogenesis Inducing Agents / pharmacology Vascular Endothelial Growth Factor Receptor-2 / metabolism Signal Transduction / drug effects Phosphatidylinositol 3-Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism Brassicaceae / chemistry Neovascularization, Physiologic / drug effects Sulfides Thiocyanates

来  源:   DOI:10.1002/ptr.8183

Abstract:
Insufficient vessel maintenance adversely impacts patients in terms of tissue reperfusion following stroke or myocardial infarction, as well as during wound healing. Angiogenesis impairment is a feature typical of metabolic disorders acting at the cardiovascular level, such as diabetes. Therapeutic angiogenesis regulation offers promising clinical implications, and natural compounds as pro-angiogenic nutraceuticals hold valuable applications in regenerative medicine. By using cultured endothelial cells from human umbilical veins (HUVEC) we studied functional and molecular responses following exposure to erucin, a natural isothiocyanate derived from Brassicaceae plants and extracted from the seeds of rocket. Erucin (at nanomolar concentrations) promotes cell migration and tube formation, similar to vascular endothelial growth factor (VEGF), through mobilizing paxillin at endothelial edges. At the molecular level, erucin induces signaling pathways typical of angiogenesis activation, namely Ras, PI3K/AKT, and ERK1/2, leading to VEGF expression and triggering its autocrine production, as pharmacological inhibition of soluble VEGF and VEGFR2 dampens endothelial functions. Furthermore, erucin, alone and together with VEGF, preserves endothelial angiogenic functions under pathological conditions, such as those induced in HUVEC by high glucose (HG) exposure. Erucin emerges as a compelling candidate for therapeutic revascularization applications, showcasing promising prospects for natural compounds in regenerative medicine, particularly in addressing angiogenesis-related disorders.
摘要:
血管维持不足对中风或心肌梗死后的组织再灌注患者产生不利影响。以及在伤口愈合期间。血管生成损害是心血管水平代谢紊乱的典型特征。比如糖尿病。治疗性血管生成调节提供了有希望的临床意义,和天然化合物作为促血管生成的营养品在再生医学中具有重要的应用价值。通过使用人脐静脉(HUVEC)培养的内皮细胞,我们研究了暴露于芥酸素后的功能和分子反应,从十字花科植物中提取的一种天然异硫氰酸盐。Erucin(在纳摩尔浓度)促进细胞迁移和管形成,与血管内皮生长因子(VEGF)相似,通过动员内皮边缘的Paxillin。在分子水平上,芥酸诱导典型的血管生成激活的信号通路,即Ras,PI3K/AKT,和ERK1/2,导致VEGF表达并触发其自分泌产生,作为可溶性VEGF和VEGFR2的药理学抑制抑制内皮功能。此外,芥酸,单独和与VEGF一起,在病理条件下保留内皮血管生成功能,例如通过高葡萄糖(HG)暴露在HUVEC中诱导的那些。Erucin成为治疗性血运重建应用的令人信服的候选者,展示了天然化合物在再生医学中的前景,特别是在解决血管生成相关疾病。
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