Acute Coronary Syndrome May be Associated with Decreased Resolvin D1-to-Leukotriene B4 Ratio.

An imbalance between inflammation-resolving lipid mediators and proinflammatory leukotrienes with the instability of atherosclerotic plaques in experimental models has been reported. However, the contribution of the balance of Resolvin D1 (RvD1) to Leukotriene B4 (LTB4) in predicting acute coronary syndrome (ACS) remains unknown. This study investigated the association of RvD1-to-LTB4 ratio with ACS.Eighty-one patients with ACS and 90 stable coronary artery disease (SCAD) patients were included in this study. Plasma RvD1 and LTB4 levels were measured with commercial kits.Patients with ACS had higher LTB4 levels, lower RvD1 levels, and a lower RvD1-to-LTB4 ratio than patients with SCAD. History of diabetes mellitus, elevated Troponin I, LTB4, and decreased RvD1-to-LTB4 ratio (odds ratio [OR]: 1.025; 95% confidence interval [CI]: 1.014-1.040; P < 0.001) were independently correlated with ACS. Receiver operating characteristic curve analysis demonstrated that RvD1-to-LTB4 ratio was a potential biomarker for the risk of ACS.A circulating proinflammatory lipid profile, characterized by a low RvD1-to-LTB4 ratio may be associated with ACS in patients with ischemic heart disease.

Simvastatin inhibits glucose uptake activity and GLUT4 translocation through suppression of the IR/IRS-1/Akt signaling in C2C12 myotubes.

Simvastatin,a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, is clinically used in the prevention and treatment of cardiovascular diseases. Numerous studies demonstrate that statins increase the risk of new-onset diabetes in long-term therapy, but mechanisms underpinning this effect are still unclear. Here, we investigated whether simvastatin inhibited the glucose uptake activity and the underlying mechanisms in C2C12 myotubes. Our studies showed that simvastatin significantly inhibited glucose uptake activity and GLUT4 translocation, whereas the effect was reversible with mevalonolactone (ML), which acts as an intermediate of cholesterol synthesis pathway. Mechanistically, the inhibition of glucose uptake and GLUT4 translocation elicited by simvastatin were associated with the suppression of the insulin receptor (IR)/IR substrate (IRS)/Akt signaling cascade. Simvastatin suppressed the phosphorylation of IR, IRS-1 and Akt, and total expression of IR or IRS-1, but did not affect Akt. Furthermore, simvastatin decreased Rac1 GTP binding. In conclusion, our findings indicate that simvastatin suppresses glucose uptake activity and GLUT4 translocation via IR-dependent IRS-1/PI3K/Akt pathway. These results provide an important new insight into the mechanism of statins on insulin sensitivity which may be associated with new-onset diabetes.