Dataset Information

Intermittent hypoxia inhibits epinephrine-induced transcriptional changes in human aortic endothelial cells.

ABSTRACT: Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular disease. While intermittent hypoxia (IH) and catecholamine release play an important role in this increased risk, the mechanisms are incompletely understood. We have recently reported that IH causes endothelial cell (EC) activation, an early phenomenon in the development of cardiovascular disease, via IH-induced catecholamine release. Here, we investigated the effects of IH and epinephrine on gene expression in human aortic ECs using RNA-sequencing. We found a significant overlap between IH and epinephrine-induced differentially expressed genes (DEGs) including enrichment in leukocyte migration, cytokine-cytokine receptor interaction, cell adhesion and angiogenesis. Epinephrine caused higher number of DEGs compared to IH. Interestingly, IH when combined with epinephrine had an inhibitory effect on epinephrine-induced gene expression. Combination of IH and epinephrine induced MT1G (Metallothionein 1G), which has been shown to be highly expressed in ECs from parts of aorta (i.e., aortic arch) where atherosclerosis is more likely to occur. In conclusion, epinephrine has a greater effect than IH on EC gene expression in terms of number of genes and their expression level. IH inhibited the epinephrine-induced transcriptional response. Further investigation of the interaction between IH and epinephrine is needed to better understand how OSA causes cardiovascular disease.

SUBMITTER: Cetin-Atalay R

PROVIDER: S-EPMC9561121 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Intermittent hypoxia inhibits epinephrine-induced transcriptional changes in human aortic endothelial cells.

Cetin-Atalay Rengul R Meliton Angelo Y AY Sun Kaitlyn A KA Glass Mariel E ME Woods Parker S PS Peng Ying-Jie YJ Fang Yun Y Hamanaka Robert B RB Prabhakar Nanduri R NR Mutlu Gökhan M GM

Scientific reports 20221013 1

Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular disease. While intermittent hypoxia (IH) and catecholamine release play an important role in this increased risk, the mechanisms are incompletely understood. We have recently reported that IH causes endothelial cell (EC) activation, an early phenomenon in the development of cardiovascular disease, via IH-induced catecholamine release. Here, we investigated the effects of IH and epinephrine on gene expression in human ...[more]

PMID: 36229484

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Project description:ObjectiveTo explore the molecular mechanism of Fuxinfang for improving injury of human aortic endothelial progenitor cells (HAECs).ObjectiveSerum samples were collected from male SD rats treated with Fuxinfang (n=8) or saline (n= 5). HAECs cultured in normoxia or hypoxic condition (2% O2) were treated with serum from normal rats or with diluted serum (1% and 10%) from rats treated with Fuxinfang. The differentially expressed genes (DEGs) between Fuxinfang-treated and control cells were detected using high-throughput sequencing to screen the target DEGs that participated in arterial endothelial cell injury and underwent changes in response to both hypoxia and Fuxinfang treatment. AmiGo and String databases were used to infer the interactions among the target genes, and the expressions of the genes were analyzed in HAECs with different treatments using enzyme-linked immunosorbent assay (ELISA) and Western blotting.ObjectiveHAECs cultured in hypoxia did not show obvious changes in cell morphology or expressions of hypoxia-related factors in response to treatment with 1% or 10% serum from Fuxinfang-treated rats. The results of high-throughput sequencing showed a total of 7134 DEGs (4205 up-regulated and 2929 down-regulated genes) in HAECs in hypoxia model group and 762 DEGs (305 upregulated and 457 down-regulated genes) in Fuxinfang-treated HAECs. Analysis of AmiGo and String databases and the constructed protein-protein interaction network identified c-Fos, NR4A1, and p38MAPK as the target genes. The results of ELISA and Western blotting showed that the expressions of c-Fos, NR4A1, p38MAPK and pp38MAPK increased significantly in cells with hypoxic exposure (P < 0.05); treatment with the serum containing Fuxinfang significantly reduced the expression levels of c-Fos, NR4A1 and p-p38MAPK in hypoxic HAECs in a concentration-dependent manner (P < 0.05).ObjectiveThe serum from Fuxinfang-treated rats can concentration-dependently inhibit the expressions of the DEGs occurring in hypoxia. Fuxinfang improves hypoxic injuries of HAECs possibly by down-regulating the expression of c-Fos to inhibit NR4A1 expression and suppressing hypoxia-induced p38 phosphorylation.

Dataset Information

Intermittent hypoxia inhibits epinephrine-induced transcriptional changes in human aortic endothelial cells.

Publications

Intermittent hypoxia inhibits epinephrine-induced transcriptional changes in human aortic endothelial cells.

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