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Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis.
FASEB J. 2014 Jul; 28(7):3197-204.FJ

Abstract

Endothelial dysfunction is defined as impairment of the balance between endothelium-dependent vasodilation and constriction. Despite evidence of uric acid-induced endothelial dysfunction, a relationship with insulin resistance has not been clearly established. In this study, we investigated the role of vascular insulin resistance in uric acid-induced endothelial dysfunction. Uric acid inhibited insulin-induced endothelial nitric oxide synthase (eNOS) phosphorylation and NO production more substantially than endothelin-1 expression in HUVECs, with IC50 of 51.0, 73.6, and 184.2, respectively. Suppression of eNOS phosphorylation and NO production by uric acid was PI3K/Akt-dependent, as verified by the transfection with p110. Treatment of rats with the uricase inhibitor allantoxanamide induced mild hyperuricemia and increased mean arterial pressure by 25%. While hyperuricemic rats did not show systemic insulin resistance, they showed impaired vasorelaxation induced by insulin by 56%. A compromised insulin response in terms of the Akt/eNOS pathway was observed in the aortic ring of hyperuricemic rats. Coadministration with allopurinol reduced serum uric acid levels and blood pressure and restored the effect of insulin on Akt-eNOS pathway and vasorelaxation. Taken together, uric acid induced endothelial dysfunction by contributing to vascular insulin resistance in terms of insulin-induced NO production, potentially leading to the development of hypertension.-Choi, Y.-J., Yoon, Y., Lee, K.-Y., Hien, T. T., Kang, K. W., Kim, K.-C., Lee, J., Lee, M.-Y., Lee, S. M., Kang, D.-H., Lee, B.-H. Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis.

Authors+Show Affiliations

College of Pharmacy, Research Institute of Pharmaceutical Sciences, and.College of Pharmacy, Research Institute of Pharmaceutical Sciences, and.College of Pharmacy, Research Institute of Pharmaceutical Sciences, and.College of Pharmacy, Research Institute of Pharmaceutical Sciences, and.College of Pharmacy, Research Institute of Pharmaceutical Sciences, and.College of Pharmacy, Research Institute of Pharmaceutical Sciences, and.College of Pharmacy, Research Institute of Pharmaceutical Sciences, and.College of Pharmacy, Dongguk University, Goyang, Republic of Korea;Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Republic of Korea; Department of Obstetrics and Gynecology, Seoul Metropolitan Boramae Medical Center, Seoul, Republic of Korea; and.Division of Nephrology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Republic of Korea.College of Pharmacy, Research Institute of Pharmaceutical Sciences, and lee@snu.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24652948

Citation

Choi, You-Jin, et al. "Uric Acid Induces Endothelial Dysfunction By Vascular Insulin Resistance Associated With the Impairment of Nitric Oxide Synthesis." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 28, no. 7, 2014, pp. 3197-204.
Choi YJ, Yoon Y, Lee KY, et al. Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis. FASEB J. 2014;28(7):3197-204.
Choi, Y. J., Yoon, Y., Lee, K. Y., Hien, T. T., Kang, K. W., Kim, K. C., Lee, J., Lee, M. Y., Lee, S. M., Kang, D. H., & Lee, B. H. (2014). Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 28(7), 3197-204. https://doi.org/10.1096/fj.13-247148
Choi YJ, et al. Uric Acid Induces Endothelial Dysfunction By Vascular Insulin Resistance Associated With the Impairment of Nitric Oxide Synthesis. FASEB J. 2014;28(7):3197-204. PubMed PMID: 24652948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis. AU - Choi,You-Jin, AU - Yoon,Yujin, AU - Lee,Kang-Yo, AU - Hien,Tran Thi, AU - Kang,Keon Wook, AU - Kim,Kyong-Cheol, AU - Lee,Jeewoo, AU - Lee,Moo-Yeol, AU - Lee,Seung Mi, AU - Kang,Duk-Hee, AU - Lee,Byung-Hoon, Y1 - 2014/03/20/ PY - 2014/3/22/entrez PY - 2014/3/22/pubmed PY - 2014/9/26/medline KW - eNOS KW - hypertension SP - 3197 EP - 204 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J VL - 28 IS - 7 N2 - Endothelial dysfunction is defined as impairment of the balance between endothelium-dependent vasodilation and constriction. Despite evidence of uric acid-induced endothelial dysfunction, a relationship with insulin resistance has not been clearly established. In this study, we investigated the role of vascular insulin resistance in uric acid-induced endothelial dysfunction. Uric acid inhibited insulin-induced endothelial nitric oxide synthase (eNOS) phosphorylation and NO production more substantially than endothelin-1 expression in HUVECs, with IC50 of 51.0, 73.6, and 184.2, respectively. Suppression of eNOS phosphorylation and NO production by uric acid was PI3K/Akt-dependent, as verified by the transfection with p110. Treatment of rats with the uricase inhibitor allantoxanamide induced mild hyperuricemia and increased mean arterial pressure by 25%. While hyperuricemic rats did not show systemic insulin resistance, they showed impaired vasorelaxation induced by insulin by 56%. A compromised insulin response in terms of the Akt/eNOS pathway was observed in the aortic ring of hyperuricemic rats. Coadministration with allopurinol reduced serum uric acid levels and blood pressure and restored the effect of insulin on Akt-eNOS pathway and vasorelaxation. Taken together, uric acid induced endothelial dysfunction by contributing to vascular insulin resistance in terms of insulin-induced NO production, potentially leading to the development of hypertension.-Choi, Y.-J., Yoon, Y., Lee, K.-Y., Hien, T. T., Kang, K. W., Kim, K.-C., Lee, J., Lee, M.-Y., Lee, S. M., Kang, D.-H., Lee, B.-H. Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/24652948/Uric_acid_induces_endothelial_dysfunction_by_vascular_insulin_resistance_associated_with_the_impairment_of_nitric_oxide_synthesis_ DB - PRIME DP - Unbound Medicine ER -