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.

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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.

Background Both disseminated intravascular coagulation and thrombotic microangiopathy are complications of sepsis as Salmonella septicemia, respectively. They are related and have similar clinical characteristics as thrombopenia and organ dysfunctions. They rarely co-occur in some specific cases, which requires a clear distinction. Case presentation A 22-year-old woman had just undergone intracranial surgery and suffered from Salmonella derby septicemia with multiorgan involvement in the hospital. Laboratory workup demonstrated coagulation disorder, hemolytic anemia, thrombocytopenia, and acute kidney injury, leading to the co-occurrence of disseminated intravascular coagulation and secondary thrombotic microangiopathy. She received antibiotics, plasma exchange therapy, dialysis, mechanical ventilation, fluids, and vasopressors and gained full recovery without complications. Conclusion Disseminated intravascular coagulation and secondary thrombotic microangiopathy can co-occur in Salmonella derby septicemia. They should be treated cautiously in diagnosis and differential diagnosis. Thrombotic microangiopathy should not be missed just because of the diagnosis of disseminated intravascular coagulation. Proper and timely identification of thrombotic microangiopathy with a diagnostic algorithm is essential for appropriate treatment and better outcomes.

High uric acid (HUA) is associated with insulin resistance and abnormal glucose metabolism in cardiomyocytes. Metformin is a recognized agonist of AMP-activated protein kinase (AMPK) and an antidiabetic drug widely used for type 2 diabetes. It can play a cardioprotective role in many pathways. We investigated whether metformin protects against HUA-induced insulin resistance and abnormal glucose metabolism in cardiomyocytes. We exposed primary cardiomyocytes to HUA, and cellular glucose uptake was quantified by measuring the uptake of 2-NBDG, a fluorescent glucose analog, after insulin excitation. Treatment with metformin (10 μmol/L) protected against HUA-inhibited glucose uptake induced by insulin in primary cardiomyocytes, as shown by fluorescence microscopy and flow cytometry analysis. HUA directly inhibited the phosphorylation of Akt and the translocation of glucose transporter type 4 (GLUT4) induced by insulin, which was blocked by metformin. Metformin promoted phosphorylation of AMPK, renewed HUA-inhibited glucose uptake induced by insulin and protected against insulin resistance in cardiomyocytes. As a result of these effects, in a mouse model of acute hyperuricemia, metformin improved insulin tolerance and glucose tolerance, accompanied by increased AMPK phosphorylation, Akt phosphorylation and translocation of GLUT4 in myocardial tissues. As expected, AICAR, another AMPK activator, had equivalent effects to metformin, demonstrating the important role of AMPK activation in protecting against insulin resistance induced by HUA in cardiomyocytes. Metformin protects against insulin resistance induced by HUA in cardiomyocytes and improves insulin tolerance and glucose tolerance in an acute hyperuricemic mouse model, along with the activation of AMPK. Consequently, metformin may be an important potential new treatment strategy for hyperuricemia-related cardiovascular disease.

High uric acid (HUA) is associated with insulin resistance and abnormal glucose metabolism in cardiomyocytes. Metformin is a recognized agonist of AMP-activated protein kinase (AMPK) and an antidiabetic drug widely used for type 2 diabetes. It can play a cardioprotective role in many pathways. We investigated whether metformin protects against HUA-induced insulin resistance and abnormal glucose metabolism in cardiomyocytes. We exposed primary cardiomyocytes to HUA, and cellular glucose uptake was quantified by measuring the uptake of 2-NBDG, a fluorescent glucose analog, after insulin excitation. Treatment with metformin (10 μmol/L) protected against HUA-inhibited glucose uptake induced by insulin in primary cardiomyocytes, as shown by fluorescence microscopy and flow cytometry analysis. HUA directly inhibited the phosphorylation of Akt and the translocation of glucose transporter type 4 (GLUT4) induced by insulin, which was blocked by metformin. Metformin promoted phosphorylation of AMPK, renewed HUA-inhibited glucose uptake induced by insulin and protected against insulin resistance in cardiomyocytes. As a result of these effects, in a mouse model of acute hyperuricemia, metformin improved insulin tolerance and glucose tolerance, accompanied by increased AMPK phosphorylation, Akt phosphorylation and translocation of GLUT4 in myocardial tissues. As expected, AICAR, another AMPK activator, had equivalent effects to metformin, demonstrating the important role of AMPK activation in protecting against insulin resistance induced by HUA in cardiomyocytes. Metformin protects against insulin resistance induced by HUA in cardiomyocytes and improves insulin tolerance and glucose tolerance in an acute hyperuricemic mouse model, along with the activation of AMPK. Consequently, metformin may be an important potential new treatment strategy for hyperuricemia-related cardiovascular disease.

BackgroundHigh uric acid (HUA) is associated with insulin resistance and abnormal glucose metabolism in cardiomyocytes. Metformin is a recognized agonist of AMP-activated protein kinase (AMPK) and an antidiabetic drug widely used for type 2 diabetes. It can play a cardioprotective role in many pathways. We investigated whether metformin protects against HUA-induced insulin resistance and abnormal glucose metabolism in cardiomyocytes.MethodsWe exposed primary cardiomyocytes to HUA, and cellular glucose uptake was quantified by measuring the uptake of 2-NBDG, a fluorescent glucose analog, after insulin excitation.ResultsTreatment with metformin (10 µmol/L) protected against HUA-inhibited glucose uptake induced by insulin in primary cardiomyocytes, as shown by fluorescence microscopy and flow cytometry analysis. HUA directly inhibited the phosphorylation of Akt and the translocation of glucose transporter type 4 (GLUT4) induced by insulin, which was blocked by metformin. Metformin promoted phosphorylation of AMPK, renewed HUA-inhibited glucose uptake induced by insulin and protected against insulin resistance in cardiomyocytes. As a result of these effects, in a mouse model of acute hyperuricemia, metformin improved insulin tolerance and glucose tolerance, accompanied by increased AMPK phosphorylation, Akt phosphorylation and translocation of GLUT4 in myocardial tissues. As expected, AICAR, another AMPK activator, had equivalent effects to metformin, demonstrating the important role of AMPK activation in protecting against insulin resistance induced by HUA in cardiomyocytes. Metformin protects against insulin resistance induced by HUA in cardiomyocytes and improves insulin tolerance and glucose tolerance in an acute hyperuricemic mouse model, along with the activation of AMPK.ConclusionsConsequently, metformin may be an important potential new treatment strategy for hyperuricemia-related cardiovascular disease.