title: MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction.
abstract: Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose) and at various time intervals (6, 12, 24 and 48 h). miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a) to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.
authors.affiliation: Department of Biochemistry, NUS Medicine, National University of Singapore, Singapore 117596, Singapore. m.s19@nus.edu.sg.
authors.forename: Maskomani
authors.initials: M
authors.lastname: Silambarasan
authors.affiliation: Department of Biochemistry, NUS Medicine, National University of Singapore, Singapore 117596, Singapore. bchtjr@nus.edu.sg.
authors.forename: Jun Rong
authors.initials: JR
authors.lastname: Tan
authors.affiliation: Department of Biochemistry, NUS Medicine, National University of Singapore, Singapore 117596, Singapore. setyowatikd1@gis.a-star.edu.sg.
authors.forename: Dwi Setyowati
authors.initials: DS
authors.lastname: Karolina
authors.affiliation: Department of Biochemistry, NUS Medicine, National University of Singapore, Singapore 117596, Singapore. bchaa@nus.edu.sg.
authors.forename: Arunmozhiarasi
authors.initials: A
authors.lastname: Armugam
authors.affiliation: Department of Anatomy, NUS Medicine, National University of Singapore, Singapore 117594, Singapore. charanjit_kaur@nuhs.edu.sg.
authors.forename: Charanjit
authors.initials: C
authors.lastname: Kaur
authors.affiliation: Department of Biochemistry, NUS Medicine, National University of Singapore, Singapore 117596, Singapore. jeyaseelan.kandiah@monash.edu.|Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Clayton VIC 3800, Australia. jeyaseelan.kandiah@monash.edu.
authors.forename: Kandiah
authors.initials: K
authors.lastname: Jeyaseelan
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D051381:Rats
chemical_list: D035683:MicroRNAs; D020169:Caspases; D005947:Glucose
keywords: apoptosis; diabetes mellitus; endothelial dysfunction; hyperglycemia; microRNA