title: Exposure to high or low glucose levels accelerates the appearance of markers of endothelial cell senescence and induces dysregulation of nitric oxide synthase.
abstract: To test the hypothesis that aging impairs endothelial cell response to glucose stress, we utilized a human umbilical vein endothelial cell in vitro model in which clinically relevant concentrations of normal (5.5 mM), high (25 mM), and low (1.5mM) glucose were tested. With advancing population doubling, exposure to normal glucose gradually decreased endothelial nitric oxide synthase expression and activity, resulting in slow, progressive development of markers of cell senescence (by population doubling level [PDL] 44). High or low glucose treatment accelerated the appearance of markers of senescence (by ~PDL 35) along with declines in endothelial nitric oxide synthase expression and activity. Human umbilical vein endothelial cells exposed to alternating low and high glucose gave even more rapid acceleration in the appearance of markers of senescence (by ~PDL 18) and reduction in endothelial nitric oxide synthase levels. Thus, exposure to low and high glucose induces earlier appearance of markers of endothelial cell senescence and dysregulation of the nitric oxide synthase gene and protein expression and function. These findings will help to elucidate endothelial dysfunction associated with glucose intolerance and improve future therapy for diabetic seniors.
authors.affiliation: Reynolds Institute on Aging, University of Arkansas for Medical Sciences, 629 Jack Stephens Drive, Little Rock, AR 72205. weijeanne@uams.edu.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Rogers
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Gohar
authors.initials: G
authors.lastname: Azhar
authors.forename: Shaoke
authors.initials: S
authors.lastname: Luo
authors.forename: Jeanne Y
authors.initials: JY
authors.lastname: Wei
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D001616:beta-Galactosidase; D005947:Glucose
keywords: Endothelial cell senescence; High glucose.; Low glucose