Background/Aims:Clinical studies have shown that hyperuricaemia is 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 cardiomyocytes. Methods: We exposed H9c2 cardiomyocytes to HUA, then cell viability was determined by MTT assay, and reactive oxygen species' (ROS) production was detected by a fluorescence assay. Western blot analysis was used to examine phosphorylation of extracellular signal-regulated kinase (ERK), p38, phosphatidylinositol 3-kinase (PI3K) and Akt. We monitored the impact of HUA on phospho-ERK and phospho-p38 levels in myocardial tissue from an acute hyperuricaemia mouse model established by potassium oxonate treatment. Results: HUA decreased cardiomyocyte viability and increased ROS production in cardiomyocytes; pre-treatment with N-acetyl-L-cysteine, a ROS scavenger, and PD98059, an ERK inhibitor, reversed HUA-inhibited viability of cardiomyocytes. Further examination of signal transduction pathways revealed HUA-induced ROS involved in activating ERK/P38 and inhibiting PI3K/Akt in cardiomyocytes. Furthermore, the acute hyperuricaemic mouse model showed an increased phospho-ERK/p38 level in myocardial tissues. Conclusion: HUA induced oxidative damage and inhibited the viability of cardiomyocytes by activating ERK/p38 signalling, for a novel potential mechanism of hyperuricaemic-related cardiovascular disease.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

ObjectiveHypertension (HTN) and type 2 diabetes (T2DM) share common risk factors and usually co-occur. This study examined the relationship between HTN history and T2DM incidence in a cohort of Chinese hypertensive subjects.MethodsWe recruited 443 cases (T2DM and HTN) and 443 sex- and age-matched controls (HTN). The history of peak systolic blood pressure (SBP) was divided into 140-159, 160-179, and ≥ 180 mmHg, and that of peak diastolic blood pressure (DBP) was divided into 90-99, 100-109, and ≥ 110 mmHg. Multiple binary logistic regression models were used to explore the association between controlled HTN status and T2DM.ResultsCreatinine concentrations were higher in the cases than in the controls (P < 0.05). The HTN duration was longer in the cases than in the controls (14.7 years vs. 13.2 years; P < 0.05). Significant differences were also found in the history of peak SBP and DBP between the cases and controls (both P < 0.05). Creatinine, HTN duration, and family history of T2DM were risk factors for T2DM in hypertensive subjects, with odds ratios (95% confidence intervals) of 1.013 (1.004-1.022), 1.025 (1.003-1.047), and 5.119 (3.266-8.026), respectively. Compared with the lowest level of peak DBP, the odds ratio for T2DM at the highest level of peak DBP was 1.757 (1.074-2.969). Subgroups analyses showed that the effect of the history of peak DBP on T2DM was significantly modified by sex (P-interaction = 0.037).ConclusionThe highest DBP and the longest HTN duration were both independently associated with T2DM in hypertensive subjects.

No abstract