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01-04-2015

Chronic Cardiovascular Disease-Associated Gene Network Analysis in Human Umbilical Vein Endothelial Cells Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Authors: Yu Yu, Jing Qin, Di Chen, Hui Wang, Junwen Wang, Ying Yu

Published in: Cardiovascular Toxicology | Issue 2/2015

Abstract

The association of dioxin exposure with increased morbidity or mortality of chronic cardiovascular diseases (CVDs) has been established by many epidemiological studies. However, the precise global gene expression alterations caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the cardiovascular system need to be further elucidated. In this study, we profiled the gene expression of human umbilical vein endothelial cells (HUVECs) exposed to different concentrations of TCDD by high-throughput sequencing. Expression of 1,838 genes was changed significantly after TCDD stimulation. The FunDO analysis suggested that some CVDs were highly associated with TCDD treatment, including atherosclerosis, thromboangiitis obliterans, pulmonary arterial hypertension (PAH), and hypertension. KEGG pathway analysis showed that many genes in the signaling pathways of vascular smooth muscle contraction and apoptosis were altered distinctly. In addition, we revealed evidence regarding the gene network changes of chronic CVDs including atherosclerosis, thrombosis, myocardial infarction (MI), hypertension, and PAH in TCDD-exposed HUVECs. We found that gene expression of β1-adrenoceptors (ADRB1), β2-adrenoceptors (ADRB2), endothelin-converting enzyme 1 (ECE1), and endothelin-1 gene (EDN1) that are involved in the blood pressure regulation pathway decreased apparently under TCDD treatment. Moreover, the transcripts of interleukin 1 beta (IL-1β) and tumor necrosis factor α (TNFα), which are related to atherosclerosis, were up-regulated by TCDD stimulation. In addition, the transcripts of Homo sapiens collagen, type IV, alpha 1 (COL4A1), and isoforms that trigger the MI pathway were up-regulated after TCDD exposure. Finally, we found enhanced platelet-derived growth factor (PDGF) and signal transducer and activator of transcription 5 (Stat5) expression with TCDD treatment in endothelial cells, which are involved in PAH induced by vascular injury.

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Title: Chronic Cardiovascular Disease-Associated Gene Network Analysis in Human Umbilical Vein Endothelial Cells Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin
Authors: Yu Yu
Jing Qin
Di Chen
Hui Wang
Junwen Wang
Ying Yu
Publication date: 01-04-2015
Publisher: Springer US
Published in: Cardiovascular Toxicology / Issue 2/2015
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-014-9279-6

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