nach oben

Cardiovascular Toxicology

Erschienen in:

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

verfasst von: Yu Yu, Jing Qin, Di Chen, Hui Wang, Junwen Wang, Ying Yu

Erschienen in: Cardiovascular Toxicology | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

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.

Nur mit Berechtigung zugänglich

Shan, Q., Wang, J., Huang, F., Lv, X., Ma, M., & Du, Y. (2014). Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicology and Applied Pharmacology, 276, 136–146.CrossRefPubMed

Lesca, P., Perrot, N., & Peryt, B. (1994). Modulating effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on skin carcinogenesis initiated by the weak inducer 7,12-dimethylbenz(a)anthracene. Drug Metabolism and Drug Interactions, 11, 37–57.CrossRefPubMed

Pesatori, A. C., Consonni, D., Bachetti, S., Zocchetti, C., Bonzini, M., Baccarelli, A., et al. (2003). Short- and long-term morbidity and mortality in the population exposed to dioxin after the “Seveso accident”. Industrial Health, 41, 127–138.CrossRefPubMed

Bertazzi, P. A., Bernucci, I., Brambilla, G., Consonni, D., & Pesatori, A. C. (1998). The Seveso studies on early and long-term effects of dioxin exposure: A review. Environmental Health Perspectives, 106(Suppl 2), 625–633.CrossRefPubMedCentralPubMed

Pelclova, D., Fenclova, Z., Preiss, J., Prochazka, B., Spacil, J., Dubska, Z., et al. (2002). Lipid metabolism and neuropsychological follow-up study of workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. International Archives of Occupational and Environmental Health, 75(Suppl), S60–S66.PubMed

Humblet, O., Birnbaum, L., Rimm, E., Mittleman, M. A., & Hauser, R. (2008). Dioxins and cardiovascular disease mortality. Environmental Health Perspectives, 116, 1443–1448.CrossRefPubMedCentralPubMed

Dalton, T. P., Kerzee, J. K., Wang, B., Miller, M., Dieter, M. Z., Lorenz, J. N., et al. (2001). Dioxin exposure is an environmental risk factor for ischemic heart disease. Cardiovascular Toxicology, 1, 285–298.CrossRefPubMed

Arzuaga, X., Reiterer, G., Majkova, Z., Kilgore, M. W., Toborek, M., & Hennig, B. (2007). PPARalpha ligands reduce PCB-induced endothelial activation: possible interactions in inflammation and atherosclerosis. Cardiovascular Toxicology, 7, 264–272.CrossRefPubMed

Biswas, G., Srinivasan, S., Anandatheerthavarada, H. K., & Avadhani, N. G. (2008). Dioxin-mediated tumor progression through activation of mitochondria-to-nucleus stress signaling. Proceedings of the National Academy of Sciences of the United States of America, 105, 186–191.CrossRefPubMedCentralPubMed

10.

Luscher, T. F., & Barton, M. (1997). Biology of the endothelium. Clinical Cardiology, 20, II-3–II-10.

11.

Fracchiolla, N. S., Todoerti, K., Bertazzi, P. A., Servida, F., Corradini, P., Carniti, C., et al. (2011). Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects. Toxicology, 283, 18–23.CrossRefPubMed

12.

Thackaberry, E. A., Jiang, Z., Johnson, C. D., Ramos, K. S., & Walker, M. K. (2005). Toxicogenomic profile of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the murine fetal heart: modulation of cell cycle and extracellular matrix genes. Toxicological Sciences, 88, 231–241.CrossRefPubMed

13.

Sobczak, M., Dargatz, J., & Chrzanowska-Wodnicka, M. (2010). Isolation and culture of pulmonary endothelial cells from neonatal mice. Journal of Visualized Experiments, 46, 2316.PubMed

14.

Zhang, F., Xu, X., Zhou, B., He, Z., & Zhai, Q. (2011). Gene expression profile change and associated physiological and pathological effects in mouse liver induced by fasting and refeeding. PLoS ONE, 6, e27553.CrossRefPubMedCentralPubMed

15.

Audic, S., & Claverie, J. M. (1997). The significance of digital gene expression profiles. Genome Research, 7, 986–995.PubMed

16.

Ghazalpour, A., Doss, S., Yang, X., Aten, J., Toomey, E. M., Van Nas, A., et al. (2004). Thematic review series: The pathogenesis of atherosclerosis. Toward a biological network for atherosclerosis. Journal of Lipid Research, 45, 1793–1805.CrossRefPubMed

17.

Schermuly, R. T., Ghofrani, H. A., Wilkins, M. R., & Grimminger, F. (2011). Mechanisms of disease: pulmonary arterial hypertension. Nature Reviews. Cardiology, 8, 443–455.CrossRefPubMed

18.

Zhang, L. Q., Cheranova, D., Gibson, M., Ding, S., Heruth, D. P., Fang, D., et al. (2012). RNA-seq reveals novel transcriptome of genes and their isoforms in human pulmonary microvascular endothelial cells treated with thrombin. PLoS ONE, 7, e31229.CrossRefPubMedCentralPubMed

19.

Yue, P., Melamud, E., & Moult, J. (2006). SNPs3D: Candidate gene and SNP selection for association studies. BMC Bioinformatics, 7, 166.CrossRefPubMedCentralPubMed

20.

Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., et al. (2003). Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Research, 13, 2498–2504.CrossRefPubMedCentralPubMed

21.

Patterson, D. G, Jr, Needham, L. L., Pirkle, J. L., Roberts, D. W., Bagby, J., Garrett, W. A., et al. (1988). Correlation between serum and adipose tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in 50 persons from Missouri. Archives of Environmental Contamination and Toxicology, 17, 139–143.CrossRefPubMed

22.

DeVito, M. J., Birnbaum, L. S., Farland, W. H., & Gasiewicz, T. A. (1995). Comparisons of estimated human body burdens of dioxin-like chemicals and TCDD body burdens in experimentally exposed animals. Environmental Health Perspectives, 103, 820–831.CrossRefPubMedCentralPubMed

23.

Morales-Hernández, A., Sánchez-Martín, F. J., Hortigón-Vinagre, M. P., Henao, F., & Merino, J. M. (2012). 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptosis by disruption of intracellular calcium homeostasis in human neuronal cell line SHSY5Y. Apoptosis, 17, 1170–1181.CrossRefPubMed

24.

Furuhata, S., Ando, K., Oki, M., Aoki, K., Ohnishi, S., Aoyagi, K., et al. (2007). Gene expression profiles of endothelial progenitor cells by oligonucleotide microarray analysis. Molecular and Cellular Biochemistry, 298, 125–138.CrossRefPubMed

25.

Dekker, R. J., Boon, R. A., Rondaij, M. G., Kragt, A., Volger, O. L., Elderkamp, Y. W., et al. (2006). KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium. Blood, 107, 4354–4363.CrossRefPubMed

26.

Beedanagari, S. R., Bebenek, I., Bui, P., & Hankinson, O. (2009). Resveratrol inhibits dioxin-induced expression of human CYP1A1 and CYP1B1 by inhibiting recruitment of the aryl hydrocarbon receptor complex and RNA polymerase II to the regulatory regions of the corresponding genes. Toxicological Sciences, 110, 61–67.CrossRefPubMedCentralPubMed

27.

Zheng, H., Xue, S., Lian, F., & Wang, Y. Y. (2011). A novel promising therapy for vein graft restenosis: overexpressed Nogo-B induces vascular smooth muscle cell apoptosis by activation of the JNK/p38 MAPK signaling pathway. Medical Hypotheses, 77, 278–281.CrossRefPubMed

28.

Acevedo, L., Yu, J., Erdjument-Bromage, H., Miao, R. Q., Kim, J. E., Fulton, D., et al. (2004). A new role for Nogo as a regulator of vascular remodeling. Nature Medicine, 10, 382–388.CrossRefPubMed

29.

Ehret, G. B., Munroe, P. B., Rice, K. M., Bochud, M., Johnson, A. D., Chasman, D. I., et al. (2011). Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature, 478, 103–109.CrossRefPubMed

30.

Ross, R. (1999). Atherosclerosis—an inflammatory disease. New England Journal of Medicine, 340, 115–126.CrossRefPubMed

31.

Figarola, J. L., Singhal, J., Rahbar, S., Awasthi, S., & Singhal, S. S. (2014). LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells. Apoptosis, 19, 776–788.CrossRefPubMed

32.

Pelclova, D., Prazny, M., Skrha, J., Fenclova, Z., Kalousova, M., Urban, P., et al. (2007). 2,3,7,8-TCDD exposure, endothelial dysfunction and impaired microvascular reactivity. Human and Experimental Toxicology, 26, 705–713.CrossRefPubMed

33.

Aragon, A. C., Goens, M. B., Carbett, E., & Walker, M. K. (2008). Perinatal 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure sensitizes offspring to angiotensin II-induced hypertension. Cardiovascular Toxicology, 8, 145–154.CrossRefPubMedCentralPubMed

34.

Denison, M. S., Rogers, J. M., Rushing, S. R., Jones, C. L., Tetangco, S. C., & Heath-Pagliuso, S. (2002). Analysis of the aryl hydrocarbon receptor (AhR) signal transduction pathway. Curr Protoc Toxicol Chapter, 4(Unit4), 8.

35.

Amara, I. E., & El-Kadi, A. O. (2011). Transcriptional modulation of the NAD(P)H:quinone oxidoreductase 1 by mercury in human hepatoma HepG2 cells. Free Radical Biology & Medicine, 51, 1675–1685.CrossRef

36.

Macneil, L. T., & Walhout, A. J. (2011). Gene regulatory networks and the role of robustness and stochasticity in the control of gene expression. Genome Research, 21, 645–657.CrossRefPubMedCentralPubMed

37.

Vogel, C. F., Sciullo, E., & Matsumura, F. (2004). Activation of inflammatory mediators and potential role of ah-receptor ligands in foam cell formation. Cardiovascular Toxicology, 4, 363–373.CrossRefPubMed

38.

Wu, D., Nishimura, N., Kuo, V., Fiehn, O., Shahbaz, S., Van Winkle, L., et al. (2011). Activation of aryl hydrocarbon receptor induces vascular inflammation and promotes atherosclerosis in apolipoprotein E-/- mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 31, 1260–1267.CrossRefPubMedCentralPubMed

39.

Irvine, K. M., Andrews, M. R., Fernandez-Rojo, M. A., Schroder, K., Burns, C. J., Su, S., et al. (2009). Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages. Journal of Leukocyte Biology, 85, 278–288.CrossRefPubMed

40.

Kopf, P. G., Scott, J. A., Agbor, L. N., Boberg, J. R., Elased, K. M., Huwe, J. K., et al. (2010). Cytochrome P4501A1 is required for vascular dysfunction and hypertension induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicological Sciences, 117, 537–546.CrossRefPubMedCentralPubMed

41.

Lind, P. M., Orberg, J., Edlund, U. B., Sjoblom, L., & Lind, L. (2004). The dioxin-like pollutant PCB 126 (3,3’,4,4’,5-pentachlorobiphenyl) affects risk factors for cardiovascular disease in female rats. Toxicology Letters, 150, 293–299.CrossRefPubMed

42.

Kopf, P. G., Huwe, J. K., & Walker, M. K. (2008). Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are associated with increased superoxide. Cardiovascular Toxicology, 8, 181–193.CrossRefPubMedCentralPubMed

43.

Ganna, A., Magnusson, P. K., Pedersen, N. L., de Faire, U., Reilly, M., Arnlov, J., et al. (2013). Multilocus genetic risk scores for coronary heart disease prediction. Arteriosclerosis, Thrombosis, and Vascular Biology, 33, 2267–2272.CrossRefPubMed

44.

Woulfe, D. S. (2010). Akt signaling in platelets and thrombosis. Expert Review of Hematology, 3, 81–91.CrossRefPubMedCentralPubMed

45.

Wikenheiser, J., Karunamuni, G., Sloter, E., Walker, M. K., Roy, D., Wilson, D. L., et al. (2013). Altering HIF-1alpha through 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure affects coronary vessel development. Cardiovascular Toxicology, 13, 161–167.CrossRefPubMedCentralPubMed

Titel: Chronic Cardiovascular Disease-Associated Gene Network Analysis in Human Umbilical Vein Endothelial Cells Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin
verfasst von: Yu Yu
Jing Qin
Di Chen
Hui Wang
Junwen Wang
Ying Yu
Publikationsdatum: 01.04.2015
Verlag: Springer US
Erschienen in: Cardiovascular Toxicology / Ausgabe 2/2015
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-014-9279-6

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

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

Abstract

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2015

The Effects of High Glucose Levels on Reactive Oxygen Species-Induced Apoptosis and Involved Signaling in Human Vascular Endothelial Cells

Creatine Supplementation Reduces Doxorubicin-Induced Cardiomyocellular Injury

Analysis of an ECG Record Database Reveals QT Interval Prolongation Potential of Famotidine in a Large Korean Population

Glyphosate-Based Herbicides Potently Affect Cardiovascular System in Mammals: Review of the Literature

Tobacco and Cardiovascular Health

Antithetical Regulation of α-Myosin Heavy Chain Between Fetal and Adult Heart Failure Though Shuttling of HDAC5 Regulating YY-1 Function