Research Paper Volume 12, Issue 18 pp 17976—17989
Prothrombotic effects of high uric acid in mice via activation of MEF2C-dependent NF-κB pathway by upregulating let-7c
- 1 Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao 266003, P.R. China
Received: January 11, 2020 Accepted: April 17, 2020 Published: September 22, 2020https://doi.org/10.18632/aging.103540
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Copyright: © 2020 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Serum uric acid is reportedly associated with thrombosis development. However, still unclear is the mechanism of high uric acid in thrombosis with the involvement of let-7c. In an aim to fill this void, we conducted this study by treating mice and human umbilical vein endothelial cells with high uric acid. Analysis indicated that let-7c was upregulated in hyperuricemia patients as well as in mice and human umbilical vein endothelial cells treated with high uric acid. Furthermore, high uric acid inhibited myocyte enhancer factor-2C, but activated nuclear factor-kappa B pathway in human umbilical vein endothelial cells. Then the targeting relationship between let-7c and myocyte enhancer factor-2C was verified. On the one hand, high uric acid shortened activated partial thromboplastin time and prothrombin time of mice and declined tissue plasminogen activator level. Additionally, the treatment prolonged thrombin time and elevated the levels of thrombosis related molecules or proteins such as Fibrinogen and D-dimer. Nevertheless, these alternations could be reversed by inhibition of let-7c and nuclear factor-kappa B pathway or overexpressing myocyte enhancer factor-2C. To sum up, our results uncovered the pro-thrombotic effect of high uric acid in mice by activating myocyte enhancer factor-2C-dependent nuclear factor-kappa B pathway via let-7c upregulation.