Unknown

Dataset Information

0

Modeling Uremic Vasculopathy With Induced Pluripotent Stem Cell-Derived Endothelial Cells as a Drug Screening System.


ABSTRACT: Background: Cardiovascular complications are the leading cause of mortality in patients with chronic kidney disease (CKD). Uremic vasculopathy plays a crucial role in facilitating the progression of cardiovascular complications in advanced CKD. However, the improvement of conventional research methods could provide further insights into CKD. Objectives: In this study, we aimed to develop a novel model of uremic vasculopathy as a potential drug screening system. Methods and Results: The effects of uremic serum and different combinations of uremic toxins on induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) of a normal control and a CKD patient were investigated using several functional assays. We found that a mixture of uremic toxins composed of high urea, creatinine, uric acid, and indoxyl sulfate exerted deleterious effects on normal control iPSC-ECs that were comparable to uremic serum by increasing reactive oxygen species and apoptosis, as well as suppression of tube formation. Additional characterization revealed a potential involvement of dysregulated TGF-? signaling as treatment with either losartan or TGF-? inhibitors led to the attenuation of adverse effects induced by uremic toxins. Importantly, impaired wound healing potential seen in CKD patient-specific iPSC-ECs was rescued by treatment with losartan and TGF-? inhibitors. Conclusion: Our study demonstrated that simplified uremic toxin mixtures can simulate the uremic micromilieu reproducibly and CKD patient-specific iPSC-ECs can potentially recapitulate susceptibility to uremic vasculopathy. This novel model of uremic vasculopathy may provide a new research tool as a drug screening system.

SUBMITTER: Jang HR 

PROVIDER: S-EPMC7835337 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

altmetric image

Publications

Modeling Uremic Vasculopathy With Induced Pluripotent Stem Cell-Derived Endothelial Cells as a Drug Screening System.

Jang Hye Ryoun HR   Cho Hyung Joon HJ   Zhou Yang Y   Shao Ning-Yi NY   Lee Kyungho K   Le Hoai Huong Thi HHT   Jeon Junseok J   Lee Jung Eun JE   Huh Wooseong W   Ong Sang-Ging SG   Lee Won Hee WH   Kim Yoon-Goo YG  

Frontiers in cell and developmental biology 20210112


<b>Background:</b> Cardiovascular complications are the leading cause of mortality in patients with chronic kidney disease (CKD). Uremic vasculopathy plays a crucial role in facilitating the progression of cardiovascular complications in advanced CKD. However, the improvement of conventional research methods could provide further insights into CKD. <b>Objectives:</b> In this study, we aimed to develop a novel model of uremic vasculopathy as a potential drug screening system. <b>Methods and Resul  ...[more]

Similar Datasets

| S-EPMC5665915 | biostudies-literature
| S-EPMC7582587 | biostudies-literature
| S-EPMC4753163 | biostudies-literature
| S-EPMC6766604 | biostudies-literature
| S-EPMC6637948 | biostudies-literature
| S-EPMC4768345 | biostudies-literature
| S-EPMC7961057 | biostudies-literature
| S-EPMC5989816 | biostudies-literature
| S-EPMC7780813 | biostudies-literature
| S-EPMC6055224 | biostudies-literature