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. 2022 Dec:173:115-117.
doi: 10.1016/j.yjmcc.2022.10.002. Epub 2022 Oct 27.

A transcriptomic atlas of drug-induced endothelial dysfunction in human endothelial cells

Chengyi Tu  1 , Yu Liu  1 , Damon R Williams  1 , Joseph C Wu  2
Affiliations

A transcriptomic atlas of drug-induced endothelial dysfunction in human endothelial cells

Chengyi Tu et al. J Mol Cell Cardiol. 2022 Dec.
No abstract available

Keywords: Chemotherapy; Drug safety; Endothelial cells; Endothelial dysfunction; Vascular injury; Vascular toxicity; iPSCs.

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Conflict of interest statement

Declaration of Competing Interest Dr. Joseph C. Wu is the co-founder and scientific advisor of Greenstone Biosciences; however, the work performed here was completely independent.

Figures

Figure 1.
Figure 1.
(A) Illustrative summary of the overall workflow and (B) dosing information of this study. Human iPSC-ECs were derived from iPSCs provided by Stanford Cardiovascular Institute Biobank and human aorta ECs were purchased from ATCC and Lonza. (C) Immunostaining of EC marker VE-cadherin in iPSC-ECs and primary aorta ECs. (D) Dose response of the 8 compounds in iPSC-ECs and primary ECs was determined using CellTiter-Glo viability assay. Cells were treated for 24 hours with increasing doses as indicated in (B). DMSO was used as the control. n=5 wells of cells for iPSC-ECs and n=6 wells of cells for primary ECs. Experiments were independently repeated twice. *p<0.05; **p<0.01; ***p<0.001. Unpaired Student’s t-test. Data are displayed as mean ± s.e.m. (E) PCA plots of 4 independent EC lines (2 iPSC-ECs and 2 human primary aorta ECs) treated with 8 compounds or DMSO for 24 hours (left) or 72 hours (right). PCA plots were generated using DESeq 2 normalized expression data of the DEGs. (F) Ranking of common pathways enriched by the upregulated DEGs and the downregulated DEGs, respectively. (G) Bubble plot of the top pathways from upregulated DEGs, including the PPAR signaling pathway, NOD-like receptor signaling pathway, fluid shear stress, and atherosclerosis in different drug treatments as well as from downregulated DEGs, including the PI3-Akt signaling, HIF-1 signaling, and AGE-RAGE signaling pathway by different drug treatments. (H) Heatmap of proteasome inhibitors-specific gene signature (24-hour time point). (I) Pathway enrichment analysis of drug-specific gene signature from the upregulated DEGs.
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