Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: The distinct role of protein kinase C and mitochondrial superoxide production
Abstract
In this study the effects of stable and intermittent high glucose concentrations on ICAM-1, VCAM-1 and E-selectin production, PKC activity and PKCbetaI, betaII and delta isoforms expression in cultured HUVEC have been examined. In stable high glucose ICAM-1, VCAM-1 and E-selectin concentration and mRNA expression increased, and this effect was even more evident in intermittent high glucose. PKC activity increased in fluctuating glucose compared to stable high glucose, due to an over-expression of betaI, betaII and delta isoforms. ICAM-1, VCAM-1 and E-selectin, after the adding of total PKC inhibitor bisindolylmaleimide-I (BIMI-I) and LY379196, a specific inhibitor of PKCbeta, were equally reduced. 8-Hydroxydeoxyguanosine (8-OHdG), a sensitive indicator of oxidative damage to DNA, increased in stable and even more in intermittent high glucose and was reduced by both BIMI-I and LY379196. However, when thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial complex II and the SOD mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) were added, all adhesion molecules, any PKC isoforms expression and 8-hydroxydeoxyguanosine were normalized in both constant and oscillating glucose. In conclusion intermittent high glucose induces a greater expression of the adhesion molecules than stable high glucose; this effect seems to be related to an activation of PKCbeta, but completely dependent from mitochondrial free radicals over-production.
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In vitro studies in human umbilical vein endothelial cells reported that increases in nitrotyrosine and 8-hydroxydeoxyguanosine were more pronounced when cells were exposed to intermittent high glucose than to constant high glucose.
“In vitro studies in human umbilical vein endothelial cells reported that increases in nitrotyrosine and 8-hydroxydeoxyguanosine, markers of oxidative stress, were more pronounced when they were exposed to intermittent high glucose than in constant high glucose.24”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [24]
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- Authors
- QUAGLIARO, L., PICONI, L., ASSALONI, R., DAROS, R., MAIER, A., ZUODAR, G., & CERIELLO, A.
- Affiliations
- University of Udine (IT)
- Corresponding author
- CERIELLO, A
- ORCID
- CERIELLO, A
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 183
- Issue
- 2
- Pages
- 259-267
- ISSN
- 0021-9150 (ISSN-L)
- OpenAlex
- W2056762166
- Cited by
- 268
- References
- 32
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 15 · 2021: 8 · 2020: 11 · 2019: 15 · 2018: 12 · 2017: 18 · 2016: 26 · 2015: 19 · 2014: 13 · 2013: 15 · 2012: 18
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Atherosclerosis (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion)
- Funders
- Novartis Pharma
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- intermittent high glucose, ICAM-1, VCAM-1, E-selectin, adhesion molecules, protein kinase C, mitochondrial superoxide, oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, endothelial cells, hyperglycemia
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Cells, Cultured, Deoxyguanosine, Dose-Response Relationship, Drug, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Glucose, Humans, Infant, Newborn, Mitochondria, Protein Kinase C, RNA, Messenger, Superoxides, Sweetening Agents, Umbilical Veins, Blotting, Northern, Blotting, Western, Gene Expression, Oxidative Stress, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, E-Selectin, In Vitro Techniques
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