Simvastatin inhibits inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages through the microRNA-22/Cyr61 axis.

Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to improve atherosclerosis (AS) via its anti-inflammatory activity. Recently, several studies have reported the involvement of macrophages in chronic inflammation associated with AS. However, it is unknown whether macrophages participate in the anti-inflammatory activity of simvastatin in AS. This study was designed to investigate the roles and underlying mechanisms of simvastatin in LPS-stimulated RAW264.7 macrophages. First, we examined the anti-inflammatory effects of simvastatin on LPS-treated macrophage RAW264.7 cells using an enzyme-linked immunosorbent assay (ELISA) and a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Then, a microarray assay was used to analyze the microRNA (miRNA) expression profile in RAW264.7 cells incubated with or without simvastatin in the presence of LPS. MicroRNA-22 (miR-22) with the highest change was validated independently by qRT-PCR. Luciferase reporter assays were conducted to determine the association between miR-22 and the cysteine-rich protein 61 (Cyr61). Subsequently, we investigated the molecular mechanism by which miR-22 functions in the anti-inflammation of simvastatin in LPS-stimulated macrophages. We found that simvastatin treatment could significantly inhibit inflammation by modulating the expression of mediators, such as IL-1ß, TNF-α and IL-6, whose expression were increased remarkably in the activated RAW264.7 cells. miR-22 was found to be one of the most significantly upregulated miRNAs in LPS-stimulated RAW264.7 macrophages after treatment with simvastatin. Pre-treatment of simvastatin in LPS-stimulated RAW264.7 macrophages enhanced miR-22 expression in a dose dependent manner. Interestingly, Cyr61, a novel pro-inflammatory factor involved in the pathogenesis of atherosclerosis (AS), was identified as a direct target of miR-22. Overexpression of miR-22 enhanced the anti-inflammatory effects of simvastatin, whereas inhibition of miR-22 had an opposite effect. More importantly, further study demonstrated that the knockdown of Cyr61 by siRNA could attenuate the inhibitory effects of miR-22 inhibition on anti-inflammatory activities of simvastatin. The results clearly show that simvastatin inhibits the inflammation response in LPS-stimulated RAW264.7 macrophages through the miR-22/Cyr61 axis and suggests that targeting the miR-22/Cyr61 axis may be a promising molecular target for AS therapy.

Beneficial effects of catheter ablation of frequent premature ventricular complexes on left ventricular function.

BACKGROUND: Frequent premature ventricular complexes (PVCs) are associated with a reversible form of LV dysfunction. OBJECTIVE: We performed a meta-analysis to evaluate the effects of catheter ablation on improvement of LV function in patients with frequent PVCs. METHODS: We searched MEDLINE for cohort studies of patients who underwent catheter ablation of frequent PVCs. LVEF both before and postablation was reported. The endpoints were changes from baseline in both LVEF and LV end-diastolic diameter (LVEDd) postablation. Quantitative analysis of continuous variables was performed according to random effect methods by MetaAnalyst Beta 3.13 software. Association between site of origin (SOO) of PVCs and degree of LVEF improvement was evaluated by meta-regression using STATA V.12.0 software. Subgroup analysis of patients with LV dysfunction at baseline was performed. RESULTS: Fifteen studies with a total of 712 patients were included. The mean PVC burden before catheter ablation was 24% (95% CI 19% to 29%). The long-term success rate of PVC ablation ranged from 66% to 90%. The overall mean increase from baseline in LVEF postablation was 7.7% (95% CI 6.1% to 9.4%) and the overall mean decrease in LVEDd was -4.6 mm (95% CI -6.0 to -3.1 mm). Meta-regression showed no significant association of SOO of PVCs with the degree of postablation LVEF improvement. Subgroup analysis showed that the overall mean increase from baseline in LVEF postablation was 12.4% (95% CI 8.1% to 16.6%) and the overall mean decrease in LVEDd was -4.8 mm (95% CI -6.2 to -3.4 mm) in patients with LV dysfunction at baseline. CONCLUSIONS: Ablation of frequent PVCs improves cardiac function, especially for patients with LV dysfunction.

A comparison of steep and shallow needle trajectories in blind axillary vein puncture.

BACKGROUND: Previously developed techniques for pacemaker lead introduction usually require some form of image guidance to facilitate the axillary vein puncture process. The existing blind vein puncture methods have not gained widespread acceptance. We aimed to investigate whether our blind vein puncture approach is effective and safe. METHODS: We compared the patient characteristics and clinical outcomes of 600 consecutive patients who underwent different blind axillary vein puncture procedures. In group I, a steep needle puncture method was used, whereas in group II a shallow needle puncture technique was used. RESULTS: The shallow needle puncture method was associated with a higher success rate than the steep needle puncture method (94% vs 54%, P < 0.00001). The shallow needle puncture method was also associated with a much shorter puncture and lead insertion time (7 ± 2 minutes vs 10 ± 3 minutes, P = 0.02). CONCLUSION: Our shallow needle puncture technique does not require any extra equipment. In addition, this method is effective and safe and may be used as the initial attempt for venous access during pacemaker implantation.