Yuanmin Li

Foam cell formation and apoptosis are closely associated with atherosclerosis pathogenesis. We determined the effect of salidroside on oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation and apoptosis in THP1 human acute monocytic leukemia cells and investigated the associated molecular mechanisms. THP1-derived macrophages were incubated with salidroside for 5 h and then exposed to ox-LDL for 24 h to induce foam cell formation. Cytotoxicity, lipid deposition, apoptosis, and the expression of various proteins were tested using the CCK8 kit, Oil Red O staining, flow cytometry, and western blotting, respectively. Ox-LDL treatment alone promoted macrophage-derived foam cell formation, while salidroside treatment alone inhibited it (p < 0.05). The number of early/late apoptotic cells decreased with salidroside treatment in a dose-dependent manner (p < 0.05). Salidroside dramatically upregulated nuclear factor erythroid 2-related factor 2, but had no effect on heme oxygenase-1 expression; moreover, it markedly downregulated ox-LDL receptor 1 and upregulated ATP-binding cassette transporter A1. Salidroside also obviously decreased the phosphorylation of JNK, ERK, p38 MAPK, and increased that of Akt. However, the total expression of these proteins was not affected. Based on our findings, we speculate that salidroside can suppress ox-LDL-induced THP1-derived foam cell formation and apoptosis, partly by regulating the MAPK and Akt signaling pathways.

Background: Fragmented QRS (fQRS) complexes are novel electrocardiographic signals, which reflect myocardial conduction delays in patients with coronary artery disease (CAD). The importance of fQRS complexes in identifying culprit vessels was evaluated in this retrospective study. Methods: A 12-lead surface electrocardiogram was obtained in 183 patients who had non-ST-elevation myocardial infarction (NSTEMI) and subsequently underwent coronary angiography (CAG). On the basis of the frequency of fQRS complexes, indices such as sensitivity, specificity, positive and negative predictive values, and likelihood ratio were evaluated to determine the ability of fQRS complexes to identify the culprit vessels. Results: Among the patients studied, elderly patients (age ≥ 65 years) and those with diabetes had a significantly higher frequency of fQRS complexes (p = 0.005, p = 0.003, respectively). The fQRS complexes recorded in the 4 precordial leads had the highest specificity (81.8%) for indentifying the culprit vessel (left anterior descending artery). However, the specificity of fQRS complexes to identify lesions in the left circumflex and right coronary arteries was lower for the inferior and lateral leads than for the limb leads (65.5% versus 71.7%); however, the limb leads had higher sensitivity (92.3% versus 89.4%). And the total sensitivity and specificity of fQRS (77.1% and 71.5%) were higher than those values for ischemic T-waves. Conclusions: The frequency of fQRS complexes was higher in elderly and diabetic patients with NSTEMI. The frequency of fQRS complexes recorded in each of the ECG leads can be used to identify culprit vessels in patients with NSTEMI.

Background: Previous studies suggested that the RhoA/ROCK pathway may contribute to vascular complications in diabetes. The present study was designed to investigate whether ROCK inhibitor fasudil could prevent high glucose-induced monocyte-endothelial cells adhesion, and whether this was related to fasudil effects on vascular endothelial cell expression of chemotactic factors, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1). Methods: HUVECs were stimulated with high glucose (HG) or HG + fasudil in different concentration or different time. Monocyte-endothelial cell adhesion was determined using fluorescence-labeled monocytes. The mRNA and protein expression of VCAM-1 and MCP-1 were measured using real-time PCR and western blot. The protein levels of RhoA, ROCKI and p-MYPT were determined using western blot analysis. ELISA was employed to measure the expression of soluble VCAM-1 and MCP-1 in cell supernatants and human serum samples. Results: Fasudil significantly suppressed HG-induced adhesion of THP-1 to HUVECs. Fasudil reduced Rho/ROCK activity (as indicated by lower p-MYPT/MYPT ratio), and prevented HG induced increases in VCAM-1 and MCP-1 mRNA and protein levels. Fasudil also decreased MCP-1 concentration in HUVEC supernatants, but increased sVCAM-1 shedding into the media. In human diabetic subjects, 2 weeks of fasudil treatment significantly decreased serum MCP-1 level from 27.9 ± 10.6 pg/ml to 13.8 ± 7.0 pg/ml (P < 0.05), while sVCAM-1 increased from 23.2 ± 7.5 ng/ml to 39.7 ± 5.6 ng/ml after fasudil treatment (P < 0.05). Conclusions: Treatment with the Rho/ROCK pathway inhibitor fasudil attenuated HG-induced monocyte-endothelial cell adhesion, possibly by reducing endothelial expression of VCAM-1 and MCP-1. These results suggest inhibition of Rho/ROCK signaling may have therapeutic potential in preventing diabetes associated vascular inflammation and atherogenesis.