Endothelial dysfunction develops gradually with age, and is the foundation of many age-related diseases in the elderly. The purpose of this study was to investigate the role of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in aging-related endothelial dysfunction. Endothelial functional parameters and biochemical indices of vascular function were examined in 2-, 6-, 12- and 24-month-old mice. Then, 6-month-old mice were administered RU.521, a specific inhibitor of cGAS, for 6 months, and endothelial functional parameters and biochemical indices of vascular function were re-examined. An in vitro model of cell senescence was established by treating human aortic endothelial cells (HAECs) with D-Galactose (D-GAL). Using inhibitors or siRNA interference, cGAS and STING were suppressed or silenced in senescent HAECs, and changes in the expression of eNOS, the senescence markers, p53, p21 and p16, components of the cGAS-STING pathway and Senescence-Associated β-galactosidase (SA-β-gal) staining were examined. Finally, cGAS, STING and p-IRF3 levels were measured in aorta tissue sections from eight patients. A decline in endothelial function, up-regulation of p53, p21 and p16 expression, and activation of the cGAS-STING pathway were observed in aging mice. Inhibition of cGAS was found to improve endothelial function and reverse the increased expression of aging markers. Our in vitro data demonstrated that D-GAL induced a decrease in eNOS expression and cell senescence, which could be partly reversed by cGAS inhibitor, STING inhibitor, siRNA-cGAS and siRNA-STING treatment. Higher expression levels of cGAS, STING and p-IRF3 were observed in aged human aortic intima tissue compared to young aortic intima tissue. Our study demonstrated that activation of the cGAS-STING pathway played a vital role in aging-related endothelial dysfunction. Thus, the cGAS-STING pathway may be a potential target for the prevention of cardiovascular diseases in the elderly.

Vascular smooth muscle cells (VSMCs) play a central role in atherosclerosis progression, but the functional changes in VSMCs and the associated cellular crosstalk during atherosclerosis progression remain unknown. Here we show that scRNA-seq analysis of proximal adjacent (PA) and atherosclerotic core (AC) regions of human carotid artery plaques identifies functional alterations in macrophage-like VSMCs, elucidating the main state differences between PA and AC VSMCs. And, IL-1β mediates macrophage-macrophage-like VSMC crosstalk through regulating key transcription factors involved in macrophage-like VSMCs functional alterations during atherosclerosis progression. In vitro assays reveal VSMCs trans-differentiated into a macrophage-like phenotype and then functional alterations in response to macrophage-derived stimuli. IL-1β promots the adhesion, inflammation, and apoptosis of macrophage-like VSMCs in a STAT3 dependent manner. The current findings provide interesting insight into the macrophages-macrophage-like VSMC crosstalk, which would drive functional alterations in the latter cell type through IL-1β/STAT3 axis during atherosclerosis progression.

Purpose: The advanced lung cancer inflammation index (ALI) is a novel inflammatory and nutritional index that exerts prognostic value in various types of cancer. A previous study demonstrated that ALI at discharge could predict the prognosis in patients with acute decompensated heart failure (ADHF). However, the long-term prognostic value of ALI on admission in elderly heart failure (HF) inpatients remains unclear.Materials and methods: We retrospectively collected HF inpatients over 65-year-old who were hospitalized in our cardiology center during the whole year of 2015. ALI was calculated as body mass index (BMI) × serum albumin (Alb)/neutrophil-to-lymphocyte ratio (NLR). Patients were divided into two groups by the optimal cutoff value of ALI for predicting all-cause mortality using time-dependent receiver operating characteristic (ROC) curves. The Spearman rank correlation coefficient was computed to evaluate the correlation between ALI and the geriatric nutritional risk index (GNRI). Kaplan–Meier curves, Cox survival analyses, time-dependent ROC analyses, and net reclassification improvement (NRI) analyses were used to assess the prognostic effect of ALI on all-cause mortality and cardiovascular mortality.Results: Over a 28-month median follow-up, all-cause and cardiovascular mortality occurred in 192 (35.4%) and 132 (24.3%) out of 543 patients, respectively. The optimal cutoff value of ALI for predicting all-cause mortality at 2 years was 25.8. Spearman’s correlation coefficient showed a moderate positive linear correlation between ALI and GNRI (r = 0.44, p < 0.001). The Kaplan–Meier analysis revealed that the cumulative incidences of both all-cause and cardiovascular mortalities were significantly higher in patients with lower ALI (log-rank test, all-cause mortality: p < 0.0001; cardiovascular mortality: p < 0.0001). The multivariate Cox proportional hazard analyses indicated that ALI was an independent predictor for both all-cause mortality (HR 0.550, 95% CI 0.349–0.867, p = 0.01) and cardiovascular mortality (HR 0.536, 95% CI 0.302–0.953, p = 0.034). Time-dependent ROC analyses showed that ALI was comparable to GNRI in predicting long-term all-cause mortality (AUC: ALI 0.625, GNRI 0.641, p = 0.976) and cardiovascular mortality (AUC: ALI 0.632, GNRI 0.626, p = 0.999) at 2 years. However, the estimated NRI indicated that the addition of ALI could not significantly improve risk stratification of base models for all-cause mortality (categorical NRI 4.9%, p = 0.433, continuous NRI 25%, p = 0.022) or cardiovascular mortality (categorical NRI 6.5%, p = 0.223, continuous NRI 27.5%, p = 0.029).Conclusion: Higher ALI was significantly associated with lower all-cause and cardiovascular mortalities in elderly HF patients. ALI on admission could be a competent nutrition-inflammation marker with independent predictive value for evaluating the long-term mortality of HF in elder population.

Although anxiety is highly prevalent after myocardial infarction (MI), but the association between anxiety and MI is not well established. This study aimed to provide an updated and comprehensive evaluation of the association between anxiety and short‐term and long‐term prognoses in patients with MI. Anxiety is associated with poor short‐term and long‐term prognoses in patients with MI. We performed a systematic search in the PubMed and Cochrane databases (January 2000–October 2020). The study endpoints were complications, all‐cause mortality, cardiac mortality, and/or major adverse cardiac events (MACEs). Pooled data were synthesized using Stata SE12.0 and expressed as risk ratios (RRs) and 95% confidence intervals (CIs). We included 9373 patients with MI from 16 published studies. Pooled analyses indicated a correlation between high anxiety and poor clinical outcomes (RR: 1.19, 95% CI: 1.13–1.26, p < .001), poor short‐term complications (RR: 1.23, 95% CI: 1.09–1.38, p = .001), and poor long‐term prognosis (RR: 1.27, 95% CI: 1.13–1.44, p < .001). Anxiety was also specifically associated with long‐term mortality (RR: 1.16, 95% CI: 1.01–1.33, p = .033) and long‐term MACEs (RR: 1.54, 95% CI: 1.26–1.90, p < .001). This study provided strong evidence that increased anxiety was associated with poor prognosis in patients with MI. Further analysis revealed that MI patients with anxiety had a 23% increased risk of short‐term complications and a 27% increased risk of adverse long‐term prognosis compared to those without anxiety.

Purpose. Cardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI). Our study aimed to evaluate the short‐term prognostic value of admission blood urea nitrogen (BUN) in patients with CS complicating AMI. Materials and Methods. 218 consecutive patients with CS after AMI were enrolled. The primary endpoint was 30‐day mortality. The association of admission BUN and 30‐day mortality and major adverse cardiovascular event (MACE) was investigated by Cox regression. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) further examined the predictive value of BUN. Results. During a period of 30‐day follow‐up, 105 deaths occurred. Compared to survivors, nonsurvivors had significantly higher admission BUN (p < 0.001), creatinine (p < 0.001), BUN/creatinine (p = 0.03), and a lower glomerular filtration rate (p < 0.001). The area under the curve (AUC) of the 4 indices for predicting 30‐day mortality was 0.781, 0.734, 0.588, and 0.773, respectively. When compared to traditional markers associated with CS, the AUC for predicting 30‐day mortality of BUN, lactate, and left ventricular ejection fraction were 0.781, 0.776, and 0.701, respectively. The optimal cut‐off value of BUN for predicting 30‐day mortality was 8.95 mmol/L with Youden‐Index analysis. Multivariate Cox analysis indicated BUN >8.95 mmol/L was an important independent predictor for 30‐day mortality (HR 2.08, 95%CI 1.28–3.36, p = 0.003) and 30‐day MACE (HR 1.85, 95%CI 1.29–2.66, p = 0.001). IDI (0.053, p = 0.005) and NRI (0.135, p = 0.010) showed an improvement in the accuracy for mortality prediction of the new model when BUN was included compared with the standard model of predictors in previous scores. Conclusion. An admission BUN >8.95 mmol/L was robustly associated with increased short‐term mortality and MACE in patients with CS after AMI. The prognostic value of BUN was superior to other renal markers and comparable to traditional markers. This easily accessible index might be promising for early risk stratification in CS patients following AMI.

Herein we provide a state-of-the-art review on the current progress of biomimetic particulate oral delivery systems.