Endothelia inflammation damage is vital to the development and progression of chronic venous disease. In the present study, we explored the protective effect of melatonin on endothelia apoptosis induced by LPS, particularly focusing on the mitochondrial fission. We demonstrated that human umbilical vein endothelial cells (HUVEC) subjected to LPS for 12 h exhibited a higher apoptotic rate. However, melatonin (1-20 μM) treatment 12 h before LPS had the ability to protect HUVEC cell against LPS-mediated apoptosis in a dose-dependent manner. Furthermore, LPS induced the cytoplasmic calcium overload which was responsible for the upregulation of calcium-dependent xanthine oxidase (XO). Higher XO expression was associated with reactive oxygen species (ROS) overproduction, leading to the Drp1 phosphorylation at the Ser616 site and migration on the surface of mitochondria. Furthermore, phosphorylated Drp1 initiated the mitochondrial fission contributing to the caspase9-dependent mitochondrial apoptosis as evidenced by lower membrane potential, more cyt-c leakage into the nuclear, and higher expression of proapoptotic proteins. However, melatonin treatment could trigger the AMPK pathway, which was followed by the increased SERCA2a expression. Activation of AMPK/SERCA2a by melatonin inhibited the calcium overload, XO-mediated ROS outburst, Drp1-required mitochondrial fission, and final mitochondrial apoptosis. In summary, this study confirmed that LPS induced HUVEC apoptosis through Ca-XO-ROS-Drp1-mitochondrial fission axis and that melatonin reduced the apoptosis of HUVEC through activation of the AMPK/SERCA2a pathway.

This model of aortic dissection using the two-end aortic intimal flap suturing method is similar to human Stanford type B aortic dissection.

To perform a meta-analysis and examine the use of D-dimer levels for diagnosing acute aortic dissection (AAD).Medline, Cochrane, EMBASE, and Google Scholar were searched until April 23, 2014, using the following search terms: biomarker, acute aortic dissection, diagnosis, and D-dimer. Inclusion criteria were diagnosis of acute aortic dissection, D-dimer levels obtained, 2-armed study. Outcome measures were the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of D-dimer level for the diagnosis of AAD. Sensitivity analysis was performed using the leave-one-out approach.Of 34 articles identified, 5 met the inclusion criteria and were included in the analysis. The age of participants was similar between treatments within studies. The number of AAD patients ranged from 16 to 107 (total = 274), and the number of control group patients ranged from 32 to 206 (total = 469). The pooled sensitivity of D-dimer levels in AAD patients was 94.5% (95% confidence interval [CI] 78.1%–98.8%, P < 0.001), and the specificity was 69.1% (95% CI 43.7%–86.5%, P = 0.136). The pooled area under the receiver-operating characteristic curve for D-dimer levels in AAD patients was 0.916 (95% CI 0.863–0.970, P < 0.001). The direction and magnitude of the combined estimates did not change markedly with the exclusion of individual studies, indicating the meta-analysis had good reliability.D-dimer levels are best used for ruling out AAD in patients with low likelihood of the disease.