Effect of uric acid on inflammatory COX-2 and ROS pathways in vascular smooth muscle cells

Abstract

Hyperuricemia is thought to play a role in cardiovascular diseases (CVD), including hypertension, coronary artery disease and atherosclerosis. However, exactly how uric acid contributes to these pathologies is unknown. An underlying mechanism of inflammatory diseases, such as atherosclerosis, includes enhanced production of cyclooxygenase-2 (COX-2) and superoxide anion. Here, we aimed to examine the effect of uric acid on inflammatory COX-2 and superoxide anion production and to determine the role of losartan. Primarily cultured vascular smooth muscle cells (VSMCs) were time and dose-dependently induced by uric acid and COX-2 and superoxide anion levels were measured. COX-2 levels were determined by ELISA, and superoxide anion was measured by the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c method. Uric acid elevated COX-2 levels in a time-dependent manner. Angiotensin-II receptor blocker, losartan, diminished uric-acid-induced COX-2 elevation. Uric acid also increased superoxide anion level in VSMCs. Uric acid plays an important role in CVD pathogenesis by inducing inflammatory COX-2 and ROS pathways. This is the first study demonstrating losartan's ability to reduce uric-acid-induced COX-2 elevation.

Synergistic therapeutic effects of Duzhong Jiangya Tablets and amlodipine besylate combination in spontaneously hypertensive rats using 1H‐NMR‐ and MS‐based metabolomics

“…Their elevated levels indicate an increase in purine metabolism. Both uric acid and allantoin are associated with oxidative stress (Lanaspa et al, 2012;Takagi et al, 2016), which can cause cardiovascular disease by inducing the production of inflammatory factors COX-2 and ROS (Oguz, Kirca, Cetin, & Yesilkaya, 2017).…”

MicroRNA-381 regulates the occurrence and immune responses of coronary atherosclerosis via cyclooxygenase-2

“…Furthermore, cyclooxygenase (COX)-2 is a key inflammatory factor in the human body. Activation of the COX-2 signaling pathway causes and aggravates the pathogenesis of atherosclerosis (11). Atherosclerosis can be considered chronic inflammation.…”

The association between hyperuricemia and coronary artery calcification development: A systematic review and meta‐analysis

“…There are several possible mechanisms that can explain the association. In vitro, uric acid has stimulated primary vascular smooth muscle cells (VSMC) to produce inflammatory cyclooxygenase‐2 and superoxide anion which contribute to the pathogenesis of atherosclerosis . In an animal model, high uric acid levels have been shown to cause premature atherosclerosis by disturbing lipid metabolism, promoting the proliferation of VSMCs, and more importantly, activating inflammation .…”