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Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression
Open accessAbstract
Recent data suggest that uric acid is generated locally in the vessel wall by the action of xanthine oxidase. This enzyme, activated during ischemia/reperfusion by proteolytic conversion of xanthine dehydrogenase, catalyzes the oxidation of xanthine, thereby generating free radicals and uric acid. Because of the potential role of ischemia/reperfusion in vascular disease, we studied the effects of uric acid on rat aortic vascular smooth muscle cell (VSMC) growth. Uric acid stimulated VSMC DNA synthesis, as measured by [3H]thymidine incorporation, in a concentration-dependent manner with half-maximal activity at 150 microM. Maximal induction of DNA synthesis by uric acid (250 microM) was approximately 70% of 10% calf serum and equal to 10 ng/ml platelet-derived growth factor (PDGF) AB or 20 ng/ml fibroblast growth factor. Neither uric acid precursors (xanthine and hypoxanthine) nor antioxidants (ascorbic acid, glutathione, and alpha-tocopherol) were mitogenic for VSMC. Uric acid was mitogenic for VSMC but not for fibroblasts or renal epithelial cells. The time course for uric acid stimulation of VSMC growth was slower than serum, suggesting induction of an autocrine growth mechanism. Exposure of quiescent VSMC to uric acid stimulated accumulation of PDGF A-chain mRNA (greater than 5-fold at 8 h) and secretion of PDGF-like material in conditioned medium (greater than 10-fold at 24 h). Uric acid-induced [3H]thymidine incorporation was markedly inhibited by incubation with anti-PDGF A-chain polyclonal antibodies. Thus uric acid stimulates VSMC growth via an autocrine mechanism involving PDGF A-chain. These findings suggest that generation of uric acid during ischemia/reperfusion contributes to atherogenesis and intimal proliferation following arterial injury.
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Cited by
Johnson, R. J., Segal, M. S., Sautin, Y., Nakagawa, T., Feig, D. I., Kang, D.-H., Gersch, M. S., Benner, S., & Sánchez-Lozada, L. G. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.4.899 · Cited by 1,075
Siu, Y.-P., Leung, K.-T., Tong, M. K.-H., & Kwan, T.-H. (2006) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2005.10.006 · Cited by 834
Sautin, Y. Y., Nakagawa, T., Zharikov, S., & Johnson, R. J. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00600.2006 · Cited by 787
Hyperuricemia and risk of stroke: A systematic review and meta‐analysis
Kim, S. Y., Guevara, J. P., Kim, K. M., Choi, H. K., Heitjan, D. F., & Albert, D. A. (2009) · Arthritis Care & Research · doi:10.1002/art.24612 · Cited by 484
Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease
Borghi, C., Agabiti-Rosei, E., Johnson, R. J., Kielstein, J. T., Lurbe, E., Mancia, G., Redon, J., Stack, A. G., & Tsioufis, K. P. (2020) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2020.07.006 · Cited by 435
Metadata
- Authors
- Rao, G. N., Corson, M. A., & Berk, B. C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1991-05
- Volume
- 266
- Issue
- 13
- Pages
- 8604-8608
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1555033960
- Cited by
- 391
- References
- 0
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Rao, G. N., Corson, M. A., & Berk, B. C. (1991). Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression. Journal of Biological Chemistry. https://doi.org/10.1016/s0021-9258(18)93017-6
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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