Homocysteine as a modulator of platelet‐derived growth factor action in vascular smooth muscle cells: a possible role for hydrogen peroxide
1997; Wiley; Volume: 122; Issue: 2 Linguagem: Inglês
10.1038/sj.bjp.0701391
ISSN1476-5381
AutoresEisuke Nishio, Yasuhiro Watanabe,
Tópico(s)Nuclear Receptors and Signaling
ResumoHomocysteine is an independent risk factor for cardiovascular disease. The mechanisms by which elevated plasma concentrations of homocysteine are related to the pathogenesis of atherosclerosis are not fully understood. Therefore, we examined the effect of homocysteine on cell replication of rat cultured vascular smooth muscle cells (VSMCs) at concentrations similar to those observed in clinical studies. The incorporation of [ 3 H]‐thymidine was used as a marker of mitosis. Homocysteine (250–500 μ M ) was a weak mitogen as compared to platelet‐derived growth factor‐BB (PDGF‐BB, 1 n M ) and serum (10%), but it potentiated the mitogenic effect of PDGF‐BB four fold at 500 μ M . This enhancement of mitogenesis was blunted by the addition of the scavenging enzyme catalase or the antioxidant N‐acetyl‐ L ‐cysteine. Furthermore, stimulation of VSMC with homocysteine (25–500 μ M ) decreased the glutathione peroxidase activity of the cells to 50% of control at 500 μ M . Inversely, homocysteine enhanced the superoxide dismutase (SOD) activity to 137% of control at 500 μ M , but it had no effect on the catalase activity. Homocysteine decreased the activity of bovine purified liver cytosolic glutathione peroxidase in a time‐ and dose‐dependent manner. The maximum decrease was 50%. In summary, homocysteine has a weak mitogenic effect on VSMC, but it dramatically enhances the mitogenic response of PDGF‐BB, presumably by disturbing the activity of antioxidant enzymes. British Journal of Pharmacology (1997) 122 , 269–274; doi: 10.1038/sj.bjp.0701391
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