Bile acids have emerged as strong signaling molecules capable of influencing various biological processes like inflammation, apoptosis, cancer progression and atherosclerosis depending on their chemistry. In the present study, we investigated the effect of major hydrophobic bile acids lithocholic acid (LCA) and deoxycholic acid (DCA) and hydrophilic bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) on angiogenesis. We employed human umbilical vein endothelial cells (HUVECs) and zebrafish embryos as model systems for studying the role of bile acids in angiogenesis. Our studies revealed that the hydrophilic CDCA enhanced ectopic vessel formation as observed by the increase in the number of sub-intestinal vessels (SIVs) in the zebrafish embryos. The pro-angiogenic role of CDCA was further corroborated by in vitro vessel formation studies performed with human umbilical vein endothelial cells (HUVECs), whereas the hydrophobic LCA reduced tubulogenesis and was toxic to the zebrafish embryos. We validated that CDCA enhances angiogenesis by increasing the expression of vascular growth factor receptors (VEGFR1 and VEGFR2) and matrix metalloproteinases (MMP9) and by decreasing the expression of adhesion protein vascular endothelial cadherin (VE-cadherin). Our work implicates that the nature of bile acids plays a critical role in dictating their biological functions and in regulating angiogenesis.

中文翻译：

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使用体外和体内模型系统，研究疏水性和亲水性胆汁酸在血管生成中的作用

胆汁酸已经作为强大的信号分子出现，取决于它们的化学性质，它们能够影响各种生物过程，例如炎症，细胞凋亡，癌症进展和动脉粥样硬化。在本研究中，我们调查了主要的疏水性胆汁酸石胆酸（LCA）和脱氧胆酸（DCA）和亲水性胆汁酸胆酸（CA）和鹅去氧胆酸（CDCA）对血管生成的影响。我们采用人脐静脉内皮细胞（HUVEC）和斑马鱼胚胎作为模型系统，研究胆汁酸在血管生成中的作用。我们的研究表明，亲水性CDCA增强了异位血管的形成，正如斑马鱼胚胎中肠下血管（SIV）数量的增加所观察到的。体外进一步证实了CDCA的促血管生成作用用人脐静脉内皮细胞（HUVEC）进行血管形成研究，而疏水性LCA减少了肾小管生成，并且对斑马鱼胚胎有毒。我们验证了CDCA通过增加血管生长因子受体（VEGFR1和VEGFR2）和基质金属蛋白酶（MMP9）的表达并通过减少粘附蛋白血管内皮钙黏着蛋白（VE-cadherin）的表达来增强血管生成。我们的工作暗示胆汁酸的性质在决定其生物学功能和调节血管生成中起着至关重要的作用。