title: Endothelial cells' biophysical, biochemical, and chromosomal aberrancies in high-glucose condition within the diabetic range.
abstract: To date, many studies have been conducted to find out the underlying mechanisms of hyperglycemia-induced complications in diabetes mellitus, attributed to the cellular pathologies of different cells-especially endothelial cells. However, there are still many ambiguities and unresolved issues to be clarified. Here, we investigated the alteration in biophysical and biochemical properties in human umbilical vein endothelial cells exposed to a high-glucose concentration (30mM), comparable to glucose content in type 2 diabetes mellitus, over a course of 120 hours. In addition to a reduction in the rate of cell viability and induction of oxidative stress orchestrated by the high-glucose condition, the dynamic of the fatty acid profile-including polyunsaturated, monounsaturated, and saturated fatty acids-was also altered in favor of saturated fatty acids. Genetic imbalances were also detected at chromosomal level in the cells exposed to the abnormal concentration of glucose after 120 hours. Moreover, the number of tip cells (CD31+/CD34+) and in vitro tubulogenesis capability negatively diminished in comparison to parallel control groups. We found that diabetic hyperglycemia was associated with a decrease in the cell-cell tight junction and upregulation in vascular endothelial cadherin and zonula occludens (ZO)-1 molecules after 72 and 120 hours of exposure to the abnormal glucose concentration, which resulted in a profound reduction in transendothelial electrical resistance. The surface plasmon resonance analysis of the human umbilical vein endothelial cells immobilized on gold-coated sensor chips confirmed the loosening of the cell to cell intercellular junction as well as stable attachment of each cell to the basal surface. Our findings highlighted the disturbing effects of a diabetic hyperglycemia on either biochemical or biophysical properties of endothelial cells.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.|Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Aysa
authors.initials: A
authors.lastname: Rezabakhsh
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Nabat
authors.affiliation: Department of Cellular and Molecular Biology, Islamic Azad University, Ahar Branch, Ahar, Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Yousefi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Soheila
authors.initials: S
authors.lastname: Montazersaheb
authors.affiliation: Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Cheraghi
authors.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Mehdizadeh
authors.affiliation: Research Center for Pharmaceutical Nanotechnology (RCPN), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Fathi
authors.affiliation: Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Movassaghpour
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Maleki-Dizaji
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.identifier: http://orcid.org/0000-0003-3864-9166
authors.initials: R
authors.lastname: Rahbarghazi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.|Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Garjani
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects*; D017097:Electric Impedance; D005227:Fatty Acids / Q000819:agonists* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D007621:Karyotyping; D008954:Models, Biological; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D018384:Oxidative Stress; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D005947:Glucose
keywords: HUVECs; biophysical and biochemical properties; cell behavior; high-glucose condition; karyotyping