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International journal of cardiology 05/2013; · 7.08 Impact Factor
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ABSTRACT: : The effects of differences among β-blockers and initiation times in patients undergoing noncardiac surgery (NCS) remain unknown. On June 1, 2012, the authors searched PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify all trials of perioperative β-blockers in patients undergoing NCS published between January 1960 and June 2012. The authors included only randomized, double-blind and placebo-controlled trials of perioperatively administered β-blockers (ie, during the pre-, intra- and/or postoperative period) in patients with at least 1 risk factor for coronary artery disease undergoing NCS. The endpoints of these trials had to include all-cause mortality, myocardial infarction (MI) and/or stroke. The authors identified 8 English-language publications, involving 11,180 patients, which fulfilled our inclusion criteria. Perioperative β-blocker therapy was associated with a significant decrease in patient risk of developing MI (relative risk [RR] = 0.73; 95% confidence interval [CI], 0.61-0.86) but a significant increase in risk of developing stroke (RR = 2.17; 95% CI, 1.35-3.50) versus placebo, resulting in a nonsignificant decrease in overall mortality (RR = 0.91; 95% CI, 0.60-1.36). Indirect comparisons demonstrated that perioperative atenolol therapy was associated with lower mortality and incidence of MI. β-blocker therapy initiated >1 week before surgery was associated with improved postoperative mortality. Perioperative β-blocker treatment of patients undergoing NCS increases the incidence of stroke but decreases the incidence of MI, leading to a nonsignificant decrease in mortality. The authors also observed that atenolol treatment or β-blocker therapy initiated >1 week before NCS was associated with improved outcomes.
The American Journal of the Medical Sciences 04/2013; · 1.39 Impact Factor
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ABSTRACT: BACKGROUND: Vaspin has insulin-sensitizing effects, as well as additional beneficial effects on metabolic diseases. However, little is known about the direct effects of vaspin on vascular complications mediated by diabetes. The objective of this study is to determine the efficacy and mechanism of vaspin on hyperglycemia-induced vascular smooth muscle cells (VSMCs) proliferation, chemokinesis and cell signaling. METHODS: Rat VSMCs proliferation was determined with 5-ethynyl-2'-deoxyuridine cell proliferation assays, chemokinesis was monitored with scratch assays, and reactive oxygen species (ROS) production was assessed using H2DCFDA and SOD-inhibited reduction of ferricytochrome c assay. Luciferase activity is assayed using a Dual Luciferase Reporter Assay System. Cell signaling is assessed by immunblotting. RESULTS: Vaspin significantly inhibited VSMCs proliferation and chemokinesis, as well as ROS generation and NADPH oxidase activity, induced by high glucose (HG) treatment. Compared with HG, vaspin significantly decreased VSMCs proliferation by 40 ± 8% at 100 ng/ml. Vaspin also decreased ROS production by 16 ± 8% at 100 ng/ml and 30 ± 8% at 300 ng/ml (all P < 0.01). Vaspin significantly abolished HG-induced phosphorylation of oxidase subunits p47phox, Akt, p38, and JNK1/2 without affecting their total levels, and attenuated HG-induced phosphorylation of insulin receptor and its downstream IRS-1 and IRS-2. For downstream targets, NF-κB activity and IκBα phosphorylation were both enhanced significantly after HG stimulation, and these effects were inhibited by vaspin. Vaspin also significantly abolished HG-induced PCNA and cyclin D1 expression. CONCLUSIONS: Vaspin inhibits HG-induced VSMCs proliferation and chemokinesis by preventing ROS activation and MAPK, PI3K/Akt, and NF-κB signaling.
Atherosclerosis 02/2013; · 3.79 Impact Factor
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ABSTRACT: 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).
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.
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).
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.
Cardiovascular Diabetology 06/2012; 11:65. · 3.35 Impact Factor
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ABSTRACT: Genome-wide association studies have identified that multiple single nucleiotide polymorphisms on chromosome 9p21 are tightly associated with coronary artery disease (CAD). However, the mechanism linking this risk locus to CAD remains unclear.
The methylation status of six candidate genes (BAX, BCL-2, TIMP3, p14(ARF), p15(INK4b) and p16(INK4a)) in 205 patients and controls who underwent coronary angiography were analyzed by quantitative MethyLight assay. Rs10757274 was genotyped and expression of INK4/ARF and antisense non-coding RNA in the INK4 locus (ANRIL) was determined by real-time RT-PCR. Compared with controls, DNA methylation levels at p15(INK4b) significantly increased in CAD patients (p = 0.006). To validate and dissect the methylation percentage of each target CpG site at p15(INK4b), pyrosequencing was performed, finding CpG +314 and +332 remarkably hypermethylated in CAD patients. Further investigation determined that p15(INK4b) hypermethylation prevalently emerged in lymphocytes of CAD patients (p = 0.013). The rs10757274 genotype was significantly associated with CAD (p = 0.003) and GG genotype carriers had a higher level of ANRIL exon 1-5 expression compared among three genotypes (p = 0.009). There was a stepwise increase in p15(INK4b) and p16(INK4a) methylation as ANRIL exon 1-5 expression elevated (r = 0.23, p = 0.001 and r = 0.24, p = 0.001, respectively), although neither of two loci methylation was directly linked to rs10757274 genotype.
p15(INK4b) methylation is associated with CAD and ANRIL expression. The epigenetic changes in p15(INK4b) methylation and ANRIL expression may involve in the mechanisms of chromosome 9p21 on CAD development.
PLoS ONE 01/2012; 7(10):e47193. · 4.09 Impact Factor
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ABSTRACT: Objective To investigate the association between low free triiodothyronine (fT3) levels and the severity and prognosis of patients with acute myocardial infarction. Methods A total of 501 patients with acute myocardial infarctions were enrolled in our study. The circulating levels of thyroid hormones and clinical parameters were assayed. The patients were categorized into either the low fT3 group or the normal fT3 group according to the fT3 level on admission. All patients underwent a follow-up for 10±2 months for mortality from any cause and the occurrence of any adverse major cardiac events (MACE). Results There were 171 patients in the low fT3 group (fT3<3.5 pmol/L) and 330 patients in the normal fT3 group (≥3.5 pmol/L). During the follow-up period, 33 patients died (6.6%) and the overall survival rates were 86.0% and 97.3% in patients with a low fT3 level and a normal fT3 level, respectively. The rates of MACE were 66.7% and 45.5% in the patients with and those without low fT3 levels, respectively. Using a multivariable Cox proportional hazards model, the fT3 level was found to be the most important predictor of cumulative death and MACE (hazard ratio [HR] for death: 0.142, p<0.001 and HR for major adverse cardiac events: 0.748, p=0.007). A Kaplan-Meier analysis revealed that those patients with low fT3 levels had higher rates of MACE and death. Conclusion A low fT3 level, a common phenomenon in patients with acute myocardial infarctions, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions.
Internal Medicine 01/2012; 51(21):3009-15. · 0.94 Impact Factor
