High ambient glucose concentration, linked to vascular complications in diabetes in vivo, modulates mRNA expression of fibronectin, collagen, tissue-type plasminogen activator, and plasminogen activator inhibitor and induces delayed replication and excess cell death in cultured vascular endothelial cells. To determine the role of high ambient glucose (30 mmol/1) in apoptosis, paired cultures of individual isolates of human umbilical vein endothelial cells (HUVECs) were exposed to both high (30 mmol/1) and low (5 mmol/1) concentrations of glucose for short-term (24, 48, and 72 h) and long-term (13 ± 1 days) experiments. Incubation of HUVECs with high glucose for >48 h increased DNA fragmentation (13.7 ± 6.5% of total DNA, mean ± SD) versus cultures kept in 5 mmol/1 glucose (10.9 ± 5.6%, P < 0.005), as measured by [3H]thymidine assays. Data were confirmed by apoptosis-specific fluorescence-activated cell sorter analysis of confluent HUVEC cultures, which displayed after long-term exposure to 30 mmol/1 glucose a 1.5-fold higher prevalence of apoptosis than control cultures exposed to 5 mmol/1 glucose (P < 0.005). In contrast, no increase in DNA fragmentation in response to 30 mmol/1 glucose was seen for standardized cell lines (K 562, P 815, YT) and fibroblasts. Expression of clusterin mRNA, originally reported to be a molecular marker of apoptosis, was only slightly affected by short-term (24-h) high-glucose exposure but was significantly reduced after long-term incubation in 30 mmol/1 glucose (82.2 ± 13.8% of control) versus 5 mmol/1 glucose, which questions the role of clusterin gene expression as a marker of apoptosis. The results demonstrate that high ambient glucose can promote apoptosis in HUVECs in vitro and suggest potential endothelial damage by hyperglycemia in diabetic patients.
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Original Articles|
November 01 1995
High-Glucose–Triggered Apoptosis in Cultured Endothelial Cells
Sabina M Baumgartner-Parzer;
Sabina M Baumgartner-Parzer
Department of Internal Medicine III, Division of Clinical Endocrinology and Metabolism, University of Vienna
Vienna, Austria
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Ludwig Wagner;
Ludwig Wagner
Department of Internal Medicine III, Division of Clinical Endocrinology and Metabolism, University of Vienna
Vienna, Austria
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Maria Pettermann;
Maria Pettermann
Department of Internal Medicine III, Division of Clinical Endocrinology and Metabolism, University of Vienna
Vienna, Austria
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Johannes Grillari;
Johannes Grillari
Department of Internal Medicine III, Division of Clinical Endocrinology and Metabolism, University of Vienna
Vienna, Austria
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Alois Gessl;
Alois Gessl
Department of Internal Medicine III, Division of Clinical Endocrinology and Metabolism, University of Vienna
Vienna, Austria
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Werner Waldhäusl
Werner Waldhäusl
Department of Internal Medicine III, Division of Clinical Endocrinology and Metabolism, University of Vienna
Vienna, Austria
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Address correspondence and reprint requests to Dr. Sabina Baumgartner-Parzer, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Waehringer Guertel 18–20, A-1090 Vienna, Austria.
1
FACS, fluorescence-activated cell sorter; FCS, fetal calf serum; HUVEC, human umbilical vein endothelial cell; SDS, sodium dodecyl sulfate; SSC, saline sodium citrate.
Diabetes 1995;44(11):1323–1327
Article history
Received:
April 04 1995
Revision Received:
July 20 1995
Accepted:
July 20 1995
PubMed:
7589831
Citation
Sabina M Baumgartner-Parzer, Ludwig Wagner, Maria Pettermann, Johannes Grillari, Alois Gessl, Werner Waldhäusl; High-Glucose–Triggered Apoptosis in Cultured Endothelial Cells. Diabetes 1 November 1995; 44 (11): 1323–1327. https://doi.org/10.2337/diab.44.11.1323
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