Abstract | BACKGROUND: Epidemiological, secondary prevention and small interventional trials suggest a preventive role of vitamin C for cardiovascular diseases (CAD), especially through improving endothelial dysfunction. Large primary prevention trials failed to confirm this. Mechanistic studies may contribute to resolve this discrepancy. AIM OF THE STUDY: METHODS: Subconfluent quiescent HUVECs were incubated with vitamin C alone or in combination with catalase (CAT) and/or hydrogenperoxide (H2O2). Intracellular MAPK were determined by Western blot, proliferation by cell count and DNA-synthesis by [3H]- thymidine-uptake. RESULTS: HUVECs were incubated with vitamin C (60 microM) for 5-60 min or for 20 min (30-90 microM). A dose-dependent phosphorylation of extracellular signal-regulated-kinases (ERKs)-1 and -2 with a maximum of phosphorylation at 15-20 min was observed and inhibitable by MEK1/2-inhibitor U0126 (5-10 microM). Vitamin C (60 microM) stimulated phosphorylation of ERK5, but not of p38 and c-Jun, demonstrating a different MAPK-activation pattern compared to H2O2. Vitamin C (60 microM) induced proliferation and a dose-dependent [3H]- thymidine-uptake (30-120 microM) within 20 h. CAT (0.3 U/ml) did neither suppress the vitamin C induced [3H]- thymidine-uptake nor ERK1/2-phosphorylation. CAT (0.3 U/ml), but not vitamin C (60 microM) abrogated the inhibitory effects of H2O2 (100 microM) on [3H]- thymidine-uptake. CONCLUSION: Physiological vitamin C-concentrations promote proliferation of subconfluent ECs by activating an ERK1/2 controlled pathway. Targeting MAPK by vitamin C may improve, besides antioxidant mechanisms, endothelial dysfunction by promoting a fast regeneration of the endothelium after tissue injury, particularly required during secondary prevention and early development.
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Authors | Gudrun Ulrich-Merzenich, Heike Zeitler, Darius Panek, Dirk Bokemeyer, Hans Vetter |
Journal | European journal of nutrition
(Eur J Nutr)
Vol. 46
Issue 2
Pg. 87-94
(Mar 2007)
ISSN: 1436-6207 [Print] Germany |
PMID | 17225921
(Publication Type: Journal Article)
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Chemical References |
- Antioxidants
- Butadienes
- Enzyme Inhibitors
- Nitriles
- Reactive Oxygen Species
- U 0126
- DNA
- Hydrogen Peroxide
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
- Ascorbic Acid
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Topics |
- Antioxidants
(pharmacology)
- Ascorbic Acid
(pharmacology)
- Blotting, Western
- Butadienes
(pharmacology)
- Cell Proliferation
(drug effects)
- DNA
(biosynthesis)
- Dose-Response Relationship, Drug
- Endothelial Cells
(drug effects)
- Enzyme Inhibitors
(pharmacology)
- Humans
- Hydrogen Peroxide
(metabolism)
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinases
(metabolism)
- Nitriles
(pharmacology)
- Phosphorylation
- Reactive Oxygen Species
(metabolism)
- Time Factors
- p38 Mitogen-Activated Protein Kinases
(metabolism)
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