Abstract
MicroRNAs (miRNAs) have been implicated in the regulation of physiological and pathophysiological processes such as vascular disease. Analysis of miRNA expression profiles in vascular disease provides new insights into the possible mechanisms underlying and therapeutic targets of disease. Acrolein is a highly reactive component of cigarette smoke, which has been implicated in the development of vascular disease. In this study, we investigated whether miRNAs play a role in the modulation of various gene expression responses to acrolein in human endothelial cells. We analyzed whole-genome miRNA and mRNA expression and found that acrolein induced differential expression of 151 miRNAs in endothelial cells. We further classified a number of target genes of the differentially expressed miRNAs. Among the differentially expressed miRNAs, miR-342-3p and 422a were upregulated, and the expression levels demonstrated a high inverse correlation with their targets, the vascular disease- related genes CLDN1 and PON1. Thus, integrating specific patterns of miRNA and mRNA levels may improve the diagnosis of vascular diseases induced by exposure to environmental pollutants such as acrolein.
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References
Gutierrez, E. et al. Endothelial dysfunction over the course of coronary artery disease. Eur. Heart J. 34, 3175–3181 (2013).
Reilly, M.P. Tobacco-related cardiovascular diseases in the 21st century. Arterioscler. Thromb. Vasc. Biol. 33, 1458–1459 (2014).
Aldini, G., Orioli, M. & Carini, M. Protein modification by acrolein: relevance to pathological conditions and inhibition by aldehyde sequestering agents. Mol. Nutr. Food Res. 55, 1301–1319 (2011).
Abraham, K. et al. Toxicology and risk assessment of acrolein in food. Mol. Nutr. Food Res. 55, 1277–1290 (2011).
Myers, C.R., Myers, J.M., Kufahl, T.D., Forbes, R. & Szadkowski, A. The effects of acrolein on the thioredoxin system: implications for redox-sensitive signaling. Mol. Nutr. Food Res. 55, 1361–1374 (2011).
Moretto, N., Volpi, G., Pastore, F. & Facchinetti, F. Acrolein effects in pulmonary cells: relevance to chronic obstructive pulmonary disease. Ann. N. Y. Acad. Sci. 1259, 39–46 (2012).
Sultana, R., Perluigi, M. & Butterfield, D.A. Lipid peroxidation triggers neurodegeneration: A redox proteomics view into the Alzheimer disease brain. Free Radic. Biol. Med. 62, 157–169 (2013).
Anderson, E.J., Katunga, L.A. & Willis, M.S. Mitochondria as a source and target of lipid peroxidation products in healthy and diseased heart. Clin. Exp. Pharmacol. Physiol. 39, 179–193 (2012).
Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004).
Zeng, Y. Principles of micro-RNA production and maturation. Oncogene 25, 6156–6162 (2006).
Hayashita, Y. et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 65, 9628–9632 (2005).
Jovanovic, M. & Hengartner, M.O. miRNAs and apoptosis: RNAs to die for. Oncogene 25, 6176–6187 (2006).
Schickel, R., Boyerinas, B., Park, S.M. & Peter, M.E. MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27, 5959–5974 (2008).
Joshi, S.R., McLendon, J.M., Comer, B.S. & Gerthoffer, W.T. MicroRNAs-control of essential genes: Implications for pulmonary vascular disease. Pulm Circ. 1, 357–364 (2011).
Sayed, A.S., **a, K., Salma, U., Yang, T. & Peng, J. Diagnosis, Prognosis and Therapeutic Role of Circulating miRNAs in Cardiovascular Diseases. Heart, Lung &Circulation 23, 503–510 (2014).
Lee, S.E. et al. MicroRNA and gene expression analysis of melatonin-exposed human breast cancer cell lines indicating involvement of the anticancer effect. J. Pineal Res. 51, 345–352 (2011).
Katoh, M. Therapeutics targeting angiogenesis: genetics and epigenetics, extracellular miRNAs and signaling networks (Review). Int. J. Mol. Med. 32, 763–767 (2013).
An, Y.R. & Hwang, S.Y. Toxicology study with micro-RNA. Mol. Cell. Toxicol. 10, 127–134 (2014).
Sumpio, B.E., Riley, J.T. & Dardik, A. Cells in focus: endothelial cell. Int. J. Biochem Cell Biol. 34, 1508–1512 (2002).
Lee, S.E. & Park, Y.S. Role of lipid peroxidation-derived alpha, beta-unsaturated aldehydes in vascular dysfunction. Oxid. Med. Cell Longev. 2013, 629028 (2013).
Dennis, G., Jr. et al. DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol. 4, P3 (2003).
Saunders, M.A. & Lim, L.P. (micro)genomic medicine microRNAs as therapeutics and biomarkers. RNA Biol. 6, 324–328 (2009).
Hoffmann, D., Melikian, A.A. & Brunnemann, K.D. Studies in tobacco carcinogenesis. IARC scientific publications 482–484 (1991).
Ranganna, K. et al. Acrolein activates mitogen-activated protein kinase signal transduction pathways in rat vascular smooth muscle cells. Mol. Cell. Biochem. 240, 83–98 (2002).
Lee, S.E. & Park, Y.S. Korean Red Ginseng water extract inhibits COX-2 expression by suppressing p38 in acrolein-treated human endothelial cells. J. Ginseng Res. 38, 34–39 (2014).
Lovell, M.A., **e, C. & Markesbery, W.R. Acrolein is increased in Alzheimer’s disease brain and is toxic to primary hippocampal cultures. Neurobiology of Aging 22, 187–194 (2001).
Puranik, R. & Celermajer, D.S. Smoking and endothelial function. Prog. Cardiovasc. Dis. 45, 443–458 (2003).
Lee, S.E. & Park, Y.S. The role of antioxidant enzymes in adaptive responses to environmental toxicants in vascular disease. Mol. Cell. Toxicol. 9, 95–101 (2013).
Park, Y.S. et al. Induction of thioredoxin reductase as an adaptive response to acrolein in human umbilical vein endothelial cells. Biochem. Biophys. Res. Commun. 327, 1058–1065 (2005).
Foncea, R., Carvajal, C., Almarza, C. & Leighton, F. Endothelial cell oxidative stress and signal transduction. Biol. Res. 33, 89–96 (2000).
Boren, T. et al. MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis. Gynecol. Oncol. 110, 206–215 (2008).
Blower, P.E. et al. MicroRNA expression profiles for the NCI-60 cancer cell panel. Mol. Cancer Ther. 6, 1483–1491 (2007).
Fickert, P., Moustafa, T. & Trauner, M. Primary sclerosing cholangitis—the arteriosclerosis of the bile duct? Lipids Health Dis. 6, 3 (2007).
Chanet, A. et al. Flavanone metabolites decrease monocyte adhesion to TNF-alpha-activated endothelial cells by modulating expression of atherosclerosis-related genes. Br. J. Nutr. 110, 587–598 (2013).
Mackness, B. & Mackness, M. Anti-inflammatory properties of paraoxonase-1 in atherosclerosis. Adv. Exp. Med. Biol. 660, 143–151 (2010).
Rozenberg, O., Rosenblat, M., Coleman, R., Shih, D.M. & Aviram, M. Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: Studies in PON1-knockout mice. Free Radic. Biol. Med. 34, 774–784 (2003).
Mackness, B., Turkie, W. & Mackness, M. Paraoxonase-1 (PON1) promoter region polymorphisms, serum PON1 status and coronary heart disease. Arch. Med. Sci. 9, 8–13 (2012).
Maloyan, A. et al. Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity. Physiol. Genomics 45, 889–900 (2013).
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Lee, S.E., Yang, H., Son, G.W. et al. Identification and characterization of MicroRNAs in acrolein-stimulated endothelial cells: Implications for vascular disease. BioChip J 9, 144–155 (2015). https://doi.org/10.1007/s13206-015-9303-3
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DOI: https://doi.org/10.1007/s13206-015-9303-3