The long-term stimulation of hyperglycemia greatly increases the incidence of vascular restenosis (RS) after angioplasty. Neointimal hyperplasia after vascular injury is the pathological cause of RS, but its mechanism has not been elucidated. MicroRNA-24 (miR-24) has low expression in the injured carotid arteries of diabetic rats. However, the role of miR-24 in the vascular system is unknown. In this study, we explore whether over-expression of miR-24 could attenuate neointimal formation in streptozotocin (STZ)-induced diabetic rats. Adenovirus (Ad-miR-24-GFP) was used to deliver the miR-24 gene to injured carotid arteries in diabetic rats. The level of neointimal hyperplasia was examined by hematoxylin-eosin (HE) staining. Vascular smooth muscle cell (VSMC) proliferation in the neointima was evaluated by immunostaining for proliferating cell nuclear antigen (PCNA). The mRNA levels of miR-24, PCNA, wingless-type MMTV integration site family member 4 (Wnt4), disheveled-1 (Dvl-1), β-catenin and cell cycle-associated molecules (Cyclin D1, p21) were determined by Quantitative Real-Time PCR (qRT-PCR). PCNA, Wnt4, Dvl-1, β-catenin, Cyclin D1 and p21 protein levels were measured by Western blotting analysis. STZ administration decreased plasma insulin and increased fasting blood glucose in Sprague-Dawley (SD) rats. The expression of miR-24 was decreased in the carotid artery after a balloon injury in diabetic rats, and adenoviral transfection (Ad-miR-24-GFP) increased the expression of miR-24. Over-expression of miR-24 suppressed VSMC proliferation and neointimal hyperplasia in diabetic rats at 14 days. Furthermore, compared with Sham group, the mRNA and protein levels of PCNA, Wnt4, Dvl-1, β-catenin, and Cyclin D1 were strikingly up-regulated in the carotid arteries of diabetic rats after a balloon injury. Interestingly, up-regulation of miR-24 significantly reduced the mRNA and protein levels of these above molecules. In contrast, the change trend in p21 mRNA and protein levels was opposite after a balloon injury. However, over-expression of miR-24 after gene delivery increased the mRNA and protein levels of p21. We conclude that over-expression of miR-24 could attenuate VSMC proliferation and neointimal hyperplasia after vascular injuries in diabetic rats. This result is possibly related to the regulation of the expression of Cyclin D1 and p21 through the Wnt4/Dvl-1/β-catenin signaling pathway.

Background: Ambient air pollution is associated with heart failure (HF), but underlying biological mechanisms remain unclear. We aimed to elucidate metabolic pathways linking air pollution exposure with HF. Methods: This prospective cohort study analysed 229 812 UK Biobank participants with nuclear magnetic resonance metabolomics data. Air pollution score was constructed by fine particulate matter, coarse particulate matter, nitrogen dioxide and nitrogen oxides. Air pollution-associated metabolic signatures were identified using elastic net regression among 251 circulating metabolites. Cox regression evaluated associations between metabolic signatures and incident HF risk. Mediation analysis quantified metabolic signatures’ role in air pollution–HF relationships. Results: During median 13.1-year follow-up, 8986 participants (3.9%) developed HF. We identified 53 metabolic metabolites reflecting air pollution exposure, comprising lipoprotein metabolism markers (22.6%), fatty acids (17.0%) and amino acids (13.2%), which were used to construct the air pollution-related metabolic signatures score. After adjustment for confounding factors, each SD increase in the metabolic signatures was associated with 8% elevated HF risk (HR 1.08, 95% CI 1.06 to 1.11). Participants in the highest quantile showed a 24% increased HF risk compared with those in the lowest quantile (HR 1.24, 95% CI 1.16 to 1.3). The metabolic signatures mediated 13.08% (95% CI 12.15% to 15.71%) of air pollution–HF associations, with lipoprotein metabolism and fatty acid signatures as primary mediators. Conclusions: Air pollution was associated with increased HF risk, with metabolic perturbations appearing to play a mediating role. These metabolic signatures provide insights into potential mechanisms linking air pollution to cardiovascular outcomes.

To evaluate the effects and safety of sacubitril/valsartan in patients with acute myocardial infarction (AMI), a total of four databases, including PubMed, Cochrane Library, Embase and Web of Science, and the ClinicalTrials.gov website were searched. Using a combination of medical subject headings and entry terms, the final search was performed in July 2021. A manual search of cross‑references from the original articles was also conducted. The meta‑analysis was subsequently performed with Revman 5.3 software and a total of four studies comprising 586 patients were included. The results disclosed a significant reduction in major adverse cardiovascular and cerebrovascular events (MACCEs) [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.30‑0.73; P=0.0007], readmission (OR, 0.45; 95% CI, 0.29‑0.71; P=0.0006), incidence of acute heart failure (AHF) (OR, 0.45; 95% CI, 0.28‑0.71; P=0.0007) and N‑terminal pro B‑type natriuretic peptide [standardized mean difference (SMD), ‑0.88; 95% CI, ‑1.55‑(‑0.21); P=0.01] in the sacubitril/valsartan group compared with that in the control group, and a random effects model was used to pool these data. No significant differences were identified in the incidence of hypotension (OR, 2.91; 95% CI, 0.55‑15.51; P=0.21), adverse events (OR, 2.19; 95% CI, 0.42‑11.37; P=0.35), left ventricular ejection fraction (mean difference, 1.96; 95% CI, ‑0.84‑4.76; P=0.17) or soluble suppression of tumorigenesis‑2 (SMD, ‑0.45; 95% CI, ‑1.62‑0.71; P=0.45) according to the random effects model.In conclusion, the present meta‑analysis revealed that sacubitril/valsartan was able to effectively reduce the incidence of MACCEs, readmission and AHF in patients with AMI after revascularization without any obvious adverse events.

Evidence on active commuting and heart failure (HF) under levels of air pollution exposure is limited, and little is known on the potential mediation roles of inflammation. The objective of this study was to investigate the association between active commuting and HF, as well as to ascertain whether air pollution may influence this relationship. This prospective study included 241,786 participants without HF at baseline in UK Biobank. The commuting mode was recorded using questionnaire. We examined long-term exposure to air pollution, including particulate matter with an aerodynamic diameter smaller than 2.5 μm (PM2.5) or 10 μm (PM10), PM2.5–10, nitrogen dioxide (NO2), and nitrogen oxide (NOx). The incident HF was identified through linkages with medical records. Cox proportional hazard models were used to estimate the association of active commuting on HF under different air pollution concentrations. Furthermore, mediation analysis was performed to test the mediated role of inflammation. A median follow-up period of 13.7 years yielded 4485 incident cases of HF. Compared with non-active commuting, both cycling (HR = 0.66, 95%CI: 0.57–0.76) and walking mode (HR = 0.86, 95%CI: 0.78–0.94) were found to be associated with the reduced risk of HF, following the full adjustment for covariates, including PM2.5. The beneficial effect of cycling (HR = 0.68, 95%CI: 0.56–0.81) and walking mode (HR = 0.82, 95%CI: 0.72–0.92) on HF was also observed in the context of high PM2.5 exposure. The inflammatory response was responsible for mediating 21.97% and 13.83% of the effect of the association between cycling mode and walking mode and HF. For those residing in regions with relatively elevated air pollution levels, active commuting may still be a viable strategy for the prevention of HF.

The purpose of this study is to explore the relationship between Life's Essential 8 (LE8) and the risk of gestational diabetes among US adults. We used National Health and Nutrition Examination Surveys 2007-2018 data to perform this study. LE8 scores comprised 4 health behaviors (diet, physical activity, nicotine exposure, and sleep duration) and 4 health factors (BMI, non-high-density lipoprotein [HDL] cholesterol, blood glucose, and blood pressure). Then, LE8 were categorized into low CVH (0 to 49 scores), moderated CVH (50 to 79 scores), and high CVH (80 to 100 scores). Weighted multivariate Logistic regression analysis model were used to estimate the relationship between LE8 and gestational diabetes. A total of 3,189 participants were included, and the portion of gestational diabetes was 15.33%, 11.46%, 7.71% in low CVH, moderate CVH, and high CVH, respectively. Adjustment for covariates, we found that high CVH (OR: 0.49, 95%CI: 0.29-0.83, p = 0.01) was associated with decreased of gestational diabetes, not moderate CVH (OR: 0.78, 95%CI: 0.50-1.20, p = 0.25). This inverse associations were dose-response dependent (p-nonlinear = 0.982). This inverse associations were significant in subgroup. Significant interaction between CVH and family diabetes with the risk of gestational diabetes was found (P for interaction = 0.04). High CVH (OR: 0.357, 95%CI: 0.176-0.724, p = 0.005) could significantly decrease the risk of gestational diabetes in the population with family diabetes. The results were generally robust in sensitivity analyses after excluding of ASCVD participants. The high CVH could decrease the risk of gestational diabetes, especially in the population of family diabetes.

We aimed to investigate the relationship between metabolomic signatures of healthy lifestyle with incident metabolic dysfunction-associated steatotic liver disease (MASLD) risk, and quantify the extent to metabolic signatures explain the healthy lifestyle-MASLD relationship. This prospective cohort study analyzed 179,261 UK Biobank participants with available nuclear magnetic resonance metabolomics data. Healthy lifestyle scores incorporated dietary quality, alcohol consumption, physical activity, and smoking behavior. Elastic net regularized regression identified lifestyle-associated metabolic signatures from 251 metabolic biomarkers. Cox regression models evaluated associations between lifestyle indices, metabolic profiles, and incident MASLD. Counterfactual-based mediation analysis quantified mechanistic pathways. During follow-up, 2422 participants (1.35%) developed incident MASLD. We identified a 94-metabolite signature strongly reflecting healthy lifestyle behaviors, dominated by lipoprotein subclasses (61.70%) and fatty acids (10.64%). Each 1-unit increment in the metabolic signature corresponded to 65.9% reduced MASLD risk (HR = 0.341, 95% CI 0.311–0.373). Mediation analysis revealed that metabolic alterations explained 55.80% (95% CI 47.85–85.28%) of the protective lifestyle-MASLD association, with fatty acid metabolism contributing the largest mediation effect. Addtionly, the parallel mediating effect of metabolic signatures, BMI, diabetes, and hypertension reached 86.21%. This comprehensive metabolomic signature captures healthy lifestyle behaviors and strongly predicts incident MASLD risk through metabolic reprogramming, particularly fatty acid and lipoprotein metabolism.