N6-methyladenosine (m6A) is one of the most prevalent, abundant, and internal transcriptional modification and plays essential roles in diverse cellular and physiological processes. Low fluid shear stress (FSS) is a key pathological factor for many cardiovascular diseases, which directly forces on the endothelial cells of vessel walls. So far, the alterations and functions of m6A modifications in vascular endothelial cells at the low FSS are still unknown. Herein, we performed the transcriptome-wide m6A modification profiling of HUVECs at different FSS. We found that the m6A modifications were altered earlier and more sensitive than mRNA expressions in response to FSS. The low FSS increased the m6A modifications at CDS region but decreased the m6A modifications at 3 ′ UTR region and regulated both the mRNA expressions and m6A modifications of the m6A regulators, such as the RBM15 and EIF3A. Functional annotations enriched by the hypermethylated and hypomethylated genes at low FSS revealed that the m6A modifications were clustered in the aging-related signaling pathways of mTOR, PI3K-AKT, insulin, and ERRB and in the oxidative stress-related transcriptional factors, such as HIF1A, NFAT5, and NFE2L2. Our study provided a pilot view of m6A modifications in vascular endothelial cells at low FSS and revealed that the m6A modifications driven by low FSS mediated the cellular responses to oxidative stress and cell aging, which suggested that the m6A modifications could be the potential targets for inhibiting vascular aging at pathological low FSS.
Objectives/Background: In the endovascular treatment of ruptured abdominal aortic aneurysm (RAAA), there is no effective evidence to show preference for a specific anesthetic option. A meta-analysis was conducted to assess the result of different anesthesia in endovascular aneurysm repair (EVAR) of RAAA.Methods: Randomized controlled trials (RCTs) and cohort studies were searched in PubMed, Embase, Ovid, and the Cochrane Library. Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool were applied to evaluate the quality of cohort studies and RCTs, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to express differences for primary and secondary outcomes. Subgroup analyses and sensitivity analyses were applied in the primary outcome to illustrate the results further. Significance was set at p < 0.05. Random-effects models were used considering limited research regardless of I 2 < 50%.Results: Ten cohort studies were included in this meta-analysis. Perioperative mortality was presented as the primary outcome by analyzing eight of these research. Among the included patients, local anesthesia (LA) was considered as a better choice considering perioperative mortality (n = 156/902) rather than general anesthesia (n = 907/3434) with significant difference (OR: 0.49; 95% CI: 0.35−0.67; p < 0.00001; I 2 = 42%). However, no significant difference was found in the secondary outcome: the complication rate, ICU admission rate, postoperative morbidity of pneumonia, myocardial infarction, leg ischemia, and wound complication.Conclusions: There exists some evidence in this review that LA appears to improve perioperative mortality, especially in hemodynamically stable patients and should be recommended for patients undergoing EVAR with RAAA when appropriate.
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