Deciphering the role of hydrophobic and hydrophilic bile acids in angiogenesis using<i>in vitro</i>and<i>in vivo</i>model systems

Kundu, Somanath; Bansal, Sandhya; Muthukumarasamy, Kalai Mangai; Sachidanandan, Chetana; Motiani, Rajender K.; Bajaj, Avinash

doi:10.1039/c7md00475c

Cited by 21 publications

(13 citation statements)

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“…Kundu et al evaluated the ability of non-conjugated bile acids to alter angiogenesis in in vitro and in vivo studies [ 28 ]. They found that the hydrophobic bile acids deoxycholic acid (DCA) and LCA inhibited tube formation and cell migration in human umbilical endothelial cells (HUVECs) in vitro, but LCA was cytotoxic to cells and could only be studied at lower, non-lethal concentrations.…”

Section: Discussionmentioning

confidence: 99%

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Glycine-Conjugated Bile Acids Protect RPE Tight Junctions against Oxidative Stress and Inhibit Choroidal Endothelial Cell Angiogenesis In Vitro

Warden

Brantley

2021

Biomolecules

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We previously demonstrated that the bile acid taurocholic acid (TCA) inhibits features of age-related macular degeneration (AMD) in vitro. The purpose of this study was to determine if the glycine-conjugated bile acids glycocholic acid (GCA), glycodeoxycholic acid (GDCA), and glycoursodeoxycholic acid (GUDCA) can protect retinal pigment epithelial (RPE) cells against oxidative damage and inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis in choroidal endothelial cells (CECs). Paraquat was used to induce oxidative stress and disrupt tight junctions in HRPEpiC primary human RPE cells. Tight junctions were assessed via transepithelial electrical resistance and ZO-1 immunofluorescence. GCA and GUDCA protected RPE tight junctions against oxidative damage at concentrations of 100–500 µM, and GDCA protected tight junctions at 10–500 µM. Angiogenesis was induced with VEGF in RF/6A macaque CECs and evaluated with cell proliferation, cell migration, and tube formation assays. GCA inhibited VEGF-induced CEC migration at 50–500 µM and tube formation at 10–500 µM. GUDCA inhibited VEGF-induced CEC migration at 100–500 µM and tube formation at 50–500 µM. GDCA had no effect on VEGF-induced angiogenesis. None of the three bile acids significantly inhibited VEGF-induced CEC proliferation. These results suggest glycine-conjugated bile acids may be protective against both atrophic and neovascular AMD.

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Section: Discussionmentioning

confidence: 99%

“…The hydrophilic bile acids CA and CDCA had differing effects on angiogenesis. CA had no effect on angiogenesis in vitro, while CDCA actually induced angiogenesis in vitro and in zebrafish [ 28 ]. Our studies have shown that taurine and glycine conjugates of CA inhibit in vitro CEC migration and tubulogenesis.…”

Section: Discussionmentioning

confidence: 99%

Glycine-Conjugated Bile Acids Protect RPE Tight Junctions against Oxidative Stress and Inhibit Choroidal Endothelial Cell Angiogenesis In Vitro

Warden

Brantley

2021

Biomolecules

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“…The present study also demonstrated that CDCA increased the expression levels of flTF and asTF in EA.hy926 cells, which indicated that CDCA may be associated with vasoconstriction. Furthermore, Kundu et al (9) demonstrated that CDCA is capable of promoting vessel formation. In a previous study, both variants were revealed to mediate various physiological and pathological functions, including angiogenesis (2).…”

Section: Discussionmentioning

confidence: 99%

“…Bile acids are strong signaling molecules that are capable of influencing various biological processes, including inflammation, apoptosis, cancer progression and atherosclerosis. Chenodeoxycholic acid (CDCA) is a bile acid that has been demonstrated to enhance ectopic vessel formation (9). Similarly, apolipoprotein M (apoM), which was discovered by Xu and Dahlbäck in 1999 (10), is mainly located in high-density lipoprotein in the blood and has been demonstrated to be associated with tumor growth, atherosclerosis and thrombosis (11–13).…”

Section: Introductionmentioning

confidence: 99%

Expression of flTF and asTF splice variants in various cell strains and tissues

Pan

et al. 2019

Mol Med Report

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Tissue factor (TF) expressed at the protein level includes two isoforms: The membrane-bound full-length TF (flTF) and the soluble alternatively spliced TF (asTF). flTF is the major thrombogenic form of TF, whereas asTF is more closely associated with tumor growth, angiogenesis, metastasis and cell growth. In order to further investigate the different expression and functions of TF splice variants, the expression of these two splice variants were detected in numerous cell strains and tissues in the present study. Quantitative polymerase chain reaction was used to measure the transcript levels of the TF variants in 11 human cell lines, including cervical cancer, breast cancer, hepatoblastoma, colorectal cancer and umbilical vein cells, and five types of tissue specimen, including placenta, esophageal cancer, breast cancer, cervical cancer (alongside normal cervical tissues) and non-small cell lung cancer (alongside adjacent and normal tissues). Furthermore, the effects of chenodeoxycholic acid (CDCA) and apolipoprotein M (apoM) on the two variants were investigated. The results demonstrated that flTF was the major form of TF, and the mRNA expression levels of flTF were higher than those of asTF in all specimens tested. CDCA significantly upregulated the mRNA expression levels of the two variants. Furthermore, overexpression of apoM promoted the expression levels of asTF in Caco-2 cells. The mRNA expression levels of asTF in cervical cancer tissues were significantly higher than in the corresponding normal tissues. To the best of our knowledge, the present study is the first to compare the expression of flTF and asTF in various samples. The results demonstrated that CDCA and apoM may modulate TF isoforms in different cell lines, and suggested that asTF may serve a role in the pathophysiological mechanism underlying cervical cancer development. In conclusion, the TF isoforms serve important and distinct roles in pathophysiological processes.

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“…This fact is exploited in targeting drugs to cancerous tissues The biological functions of bile acids depend on their chemical nature and polarity [8]. Both LCA and deoxycholic acid (DCA) are hydrophobic but show different toxicity [9]. Bajaj et al [10] have reported that DCA having two hydroxyl groups shows weak interactions with cell membranes compared to highly hydrophobic LCA.…”

Section: Introductionmentioning

confidence: 99%