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Clinical studies have shown hyperuricemia strongly associated with cardiovascular disease. However, the molecular mechanisms of high uric acid （HUA） associated with cardiovascular disease remain poorly understood. In this study, we investigated the effect of HUA on primary cardiomyocytes and H9c2 cardiomyocytes, a rat cardiomyocyte cell line.
We exposed cardiomyocytes to HUA, then cell viability was determined by MTT assay, and reactive oxygen species (ROS) production was detected by fluorescent. Western blot analysis was used to examine the levels of phosphorylated extracellular signal-regulated kinase (ERK), phospho-P38, phosphorylated phosphatidylinositol 3-kinase (PI3K) and phospho-Akt. We monitored the impact of HUA on phospho-ERK and phospho-P38 levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment.
Our data showed that HUA decreased cardiomyocytes viability and increased ROS production in cardiomyocytes; pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, and PD98059, an ERK inhibitor, reversed HUA-inhibited viability in H9c2 cardiomyocytes. Further examination on signal transduction pathways revealed that HUA-induced ROS is involved in the activation of ERK/P38 and inhibition of PI3K/Akt in cardiomyocytes. Furthermore, the acute hyperuricemic mice model showed increased phospho-ERK/P38 in myocardial tissues.
These results indicate that HUA induce oxidative damage and inhibit viability of cardiomyocytes by activating the ERK/P38 signal pathways, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease.