Vascular smooth muscle cell (VSMC) phenotypic switching plays a critical role in the formation of abdominal aortic aneurysms (AAAs). FoxO3a is a key suppressor of VSMC homeostasis. We found that in human and animal AAA tissues, FoxO3a was upregulated, SM22α and α-smooth muscle actin (α-SMA) proteins were downregulated and synthetic phenotypic markers were upregulated, indicating that VSMC phenotypic switching occurred in these diseased tissues. In addition, in cultured VSMCs, significant enhancement of FoxO3a expression was found during angiotensin II (Ang II)-induced VSMC phenotypic switching. In vivo, FoxO3a overexpression in C57BL/6J mice treated with Ang II increased the formation of AAAs, whereas FoxO3a knockdown exerted an inhibitory effect on AAA formation in ApoE−/− mice infused with Ang II. Mechanistically, FoxO3a overexpression significantly inhibited the expression of differentiated smooth muscle cell (SMC) markers, activated autophagy, the essential repressor of VSMC homeostasis, and promoted AAA formation. Our study revealed that FoxO3a promotes VSMC phenotypic switching to accelerate AAA formation through the P62/LC3BII autophagy signaling pathway and that therapeutic approaches that decrease FoxO3a expression may prevent AAA formation.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Silibinin is a flavonoid compound which has medicinal value. Previous studies revealed that silibinin exhibited an anti-fibrotic effect. However, whether silibinin could attenuate high-fat diet (HFD)-induced renal fibrosis remains unclear. Therefore, this study aimed to explore the molecular mechanism by which silibinin regulated renal fibrosis induced by HFD. Methods: In the present study, human renal glomerular endothelial cells (HRGECs) were treated with various concentrations of silibinin. Then, cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. In addition, HRGECs were exposed to 100 nM TGF-β1 for mimicking in vitro renal fibrosis. The expressions of collagen I, fibronectin, and α-SMA were detected by reverse transcription-quantitative polymerasechain reaction and Western blot. Protein levels of p-IκB and p-p65 were examined by Western blot; meanwhile, level of NF-κB was measured by immunofluorescence staining. Furthermore, HFD-induced mouse model of renal fibrosis was established. The mouse body weight, fasting glucose, kidney weight/body weight, microalbuminuria, kidney histopathology, and fibrotic area were measured to assess the severity of renal fibrosis. Results: Low concentration of silibinin (≤50 μM) had no cytotoxicity, while high concentration of silibinin (≥75 μM) exhibited significant cytotoxicity. Additionally, TGF-β1 increased the expressions of collagen I, fibronectin, α-SMA, p-IκB, and p-p65 and decreased the level NF-κB, while these effects were notably reversed by 50 μM silibinin. Moreover, both 50 and 100 mg/kg silibinin greatly decreased HFD-induced the upregulation of kidney weight/body weight, microalbuminuria, and fibrotic area. 100 mg/kg silibinin markedly reduced collagen I, fibronectin, and p-p65 expressions in mice renal tissues. Conclusion: Silibinin was able to attenuate renal fibrosis in vitro and in vivo via inhibition of NF-κB. These data suggested that silibinin may serve as a potential agent to alleviate the renal fibrosis of DN.

Background Few studies have evaluated the clinical presentation, management, and outcomes of patients with end-stage renal disease (ESRD) presenting with acute aortic dissection (AAD) in real-world clinical practice. Thus, this study investigated the clinical characteristics, management, and outcomes of AAD patients with ESRD. Methods A total of 217 patients were included. We evaluated the differences in the clinical features, management, and in-hospital outcomes of patients with and without a history of ESRD presenting with AAD. Results A history of ESRD was present in 71 of 217 patients. Patients with ESRD had atypical clinical manifestations (p < 0.001) and were more likely to be managed medically compared with patients without ESRD (p = 0.002). Hypertension and type B aortic dissection were significantly more common among patients with ESRD. Moreover, patients with ESRD had lower leucocyte and platelet counts than patients without ESRD in laboratory findings (p < 0.001). However, hospitalization days and in-hospital mortality were similar between the two groups (p > 0.05). Multivariate analysis identified Type A aortic dissection as an independent predictor of in-hospital mortality among patients without ESRD (OR, 13.68; 95% CI, 1.92 to 98.90; P = 0.006). Conclusions This study highlights differences in the clinical characteristics, management, and outcomes of AAD patients with ESRD. These patients usually have atypical symptoms and more comorbid conditions and are managed more conservatively. However, these patients have no in-hospital survival disadvantage over those without ESRD. Further studies are needed to better understand and optimize care for patients with ESRD presenting with AAD.

Aims: The purpose of this study was to evaluate the effect of angiotensin-converting enzyme inhibitors (ACEIs) on contrast-induced nephropathy (CIN) in patients undergoing coronary angiography or percutaneous coronary intervention (PCI). Methods: We searched the Medline, Embase, Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP database and Wanfang database up to December 2014. Pooled risk ratios (RRs) or weighted mean difference (WMD) with their 95% CIs for the CIN incidence, serum creatinine (SCr), estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) of the patients were collected and calculated using the software Review Manager 5.2. Results: A total of 12 separate studies including 1,868 patients (1,011 ACEI cases and 857 controls) were considered in the meta-analysis. The overall RR of the incident CIN in the ACEI group vs. the control group was 0.95 (95% CI 0.57-1.58), and the total WMDs of the ΔSCr, ΔeGFR and ΔBUN were -0.01 (95% CI -0.04 to 0.02), 5.71 (95% CI -0.66 to 12.09) and 0.78 (95% CI -0.16 to 1.73), respectively. Besides, the RR of CIN incidence in the captopril group vs. the control group was 0.72 (95% CI 0.25-2.05, p = 0.54), and the pooled WMD of the ΔSCr was -0.13 (95% CI -0.21 to -0.06, p < 0.01). Conclusion: This meta-analysis suggests that ACEIs administration has no significant influence in the CIN of patients undergoing coronary angiography or PCI; however, captopril might have the potential to prevent CIN.

BackgroundThe imbalance of gut microbiota (GM) is associated with a higher risk of thrombosis in patients with atrial fibrillation (AF). Oral anticoagulants (OACs) have been found to significantly reduce the risk of thromboembolism and increase the risk of bleeding. However, the OAC-induced alterations in gut microbiota in patients with AF remain elusive.MethodsIn this study, the microbial composition in 42 AF patients who received long-term OAC treatment (AF-OAC group), 47 AF patients who did not (AF group), and 40 volunteers with the risk of AF (control group) were analyzed by 16S rRNA gene sequencing of fecal bacterial DNA. The metagenomic functional prediction of major bacterial taxa was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software package.ResultsThe gut microbiota differed between the AF-OAC and AF groups. The abundance of Bifidobacterium and Lactobacillus decreased in the two disease groups at the genus level, but OACs treatment mitigated the decreasing tendency and increased beneficial bacterial genera, such as Megamonas. In addition, OACs reduced the abundance of pro-inflammatory taxa on the genus Ruminococcus but increased certain potential pathogenic taxa, such as genera Streptococcus, Escherichia-Shigella, and Klebsiella. The Subgroup Linear discriminant analysis effect size (LEfSe) analyses revealed that Bacteroidetes, Brucella, and Ochrobactrum were more abundant in the anticoagulated bleeding AF patients, Akkermansia and Faecalibacterium were more abundant in the non-anticoagulated-bleeding-AF patients. The neutrophil-to-lymphocyte ratio (NLR) was lower in the AF-OAC group compared with the AF group (P &lt; 0.05). Ruminococcus was positively correlated with the NLR and negatively correlated with the CHA2DS2-VASc score (P &lt; 0.05), and the OACs-enriched species (Megamonas and Actinobacteria) was positively correlated with the prothrombin time (PT) (P &lt; 0.05). Ruminococcus and Roseburia were negatively associated with bleeding events (P &lt; 0.05).ConclusionsOur study suggested that OACs might benefit AF patients by reducing the inflammatory response and modulating the composition and abundance of gut microbiota. In particular, OACs increased the abundance of some gut microbiota involved in bleeding and gastrointestinal dysfunction indicating that the exogenous supplementation with Faecalibacterium and Akkermansia might be a prophylactic strategy for AF-OAC patients to lower the risk of bleeding after anticoagulation.