With the development of the times, cardiovascular diseases have become the biggest cause of death in the global aging society, causing a serious social burden. Atherosclerosis is a chronic inflammatory disease, which can occur in large and medium‐sized blood vessels in the whole body. It takes atherosclerotic plaque as the typical pathological change and endothelial injury as the core pathophysiological mechanism. It is the pathological basis of coronary heart disease, peripheral artery disease, cerebrovascular disease, and other diseases. Recent studies have shown that chronic stress plays an important role in the occurrence and development of atherosclerosis, endothelial injury, lipid metabolism, and chronic inflammation. This process involves a large number of molecular targets. It is usually the cause of atherosclerotic cardiovascular and cerebrovascular diseases. If chronic stress factors exist for a long time, patients have genetic susceptibility, and the combination of environmental factors triggers the pathogenesis, which may eventually lead to complete blockage of the blood vessels, unstable rupture of plaques, and serious adverse cardiovascular events. This paper reviews the role of chronic stress in the occurrence and development of atherosclerosis, focusing on the pathophysiological mechanism.

Objective. Advanced glycation end products (AGEs) are featured metabolites associated with diabetic cardiomyopathy which is characterized by heart failure caused by myocyte apoptosis. Selenium was proved cardioprotective. This study was aimed at investigating the therapeutic effects and underlying mechanisms of selenium supplementation on AGE‐induced heart failure. Methods. Rats and primary myocytes were exposed to AGEs. Selenium supplementation was administrated. Cardiac functions and myocyte apoptosis were evaluated. Oxidative stress was assessed by total antioxidant capacity (TAC), reactive oxygen species (ROS) generation, and GPX activity. Expression levels of DNA methyltransferases (DNMTs) and glutathione peroxidase 1 (GPX1) were evaluated. DNA methylation of the GPX1 promoter was analyzed. Results. AGE exposure elevated intracellular ROS generation, induced myocyte apoptosis, and impaired cardiac functions. AGE exposure increased DNMT1 and DNMT2 expression, leading to the reduction of GPX1 expression and activity in the heart. Selenium supplementation decreased DNMT2 expression, recovered GPX1 expression and activity, and alleviated intracellular ROS generation and myocyte apoptosis, resulting in cardiac function recovery. DNA methylation analysis in primary myocytes indicated that selenium supplementation or DNMT inhibitor AZA treatment reduced DNA methylation of the GPX1 gene promoter. Selenium supplementation and AZA administration showed synergic inhibitory effect on GPX1 gene promoter methylation. Conclusions. Selenium supplementation showed cardioprotective effects on AGE‐induced heart failure by suppressing ROS‐mediated myocyte apoptosis. Selenium supplementation suppressed ROS generation by increasing GPX1 expression via inhibiting DNMT2‐induced GPX1 gene promoter DNA methylation in myocytes exposed to AGEs.

Background: Since myocardial work (MW) and left atrial strain are valuable for screening coronary artery disease (CAD), this study aimed to develop a novel CAD screening approach based on machine learning-enhanced echocardiography. Methods: This prospective study used data from patients undergoing coronary angiography, in which the novel echocardiography features were extracted by a machine learning algorithm. A total of 818 patients were enrolled and randomly divided into training (80%) and testing (20%) groups. An additional 115 patients were also enrolled in the validation group. Results: The superior diagnosis model of CAD was optimized using 59 echocardiographic features in a gradient-boosting classifier. This model showed that the value of the receiver operating characteristic area under the curve (AUC) was 0.852 in the test group and 0.834 in the validation group, with high sensitivity (0.952) and low specificity (0.691), suggesting that this model is very sensitive for detecting CAD, but its low specificity may increase the high false-positive rate. We also determined that the false-positive cases were more susceptible to suffering cardiac events than the true-negative cases. Conclusions: Machine learning-enhanced echocardiography can improve CAD detection based on the MW and left atrial strain features. Our developed model is valuable for estimating the pre-test probability of CAD and screening CAD patients in clinical practice. Trial registration: Registered as NCT03905200 at ClinicalTrials.gov. Registered on 5 April 2019.

Background: Acute myocardial infarction (AMI) remains a significant cause of global mortality, exacerbated by ischemia-reperfusion (IR) injury. Myocardial cell pyroptosis has emerged as a critical pathway influencing IR injury severity. Methods: We aimed to investigate the cardioprotective effects of aerobic exercise on IR injury by examining the modulation of IGFBP2 and its impact on GSDME-dependent myocardial cell pyroptosis. Mechanistic pathways were explored using western blot analysis, ELISA, immunofluorescence, and echocardiography. Results: Our findings demonstrate that aerobic exercise leads to increased circulating levels of IGFBP2, which effectively suppresses GSDME-dependent myocardial cell pyroptosis. This regulation occurs via the AKT-GSK3β signaling pathway, involving VDAC1 phosphorylation, thereby enhancing mitochondrial function and reducing oxidative stress. Conclusion: In conclusion, our study highlights the role of IGFBP2 in mitigating GSDME-dependent pyroptosis as a mechanism through which aerobic exercise exerts cardioprotective effects against IR injury. These insights suggest potential therapeutic targets for managing acute myocardial infarction.

The contemporary consensus firmly emphasizes the urgent need to reorient research efforts toward the early detection of preclinical Alzheimer’s disease (AD) or mild cognitive impairment (MCI). However, there is still a notable absence of novel biomarkers that are both efficient, minimally invasive, and cost-effective in real-world clinical settings. To address this gap, datasets GSE29378 and GSE12685 were selected to screen differentially expressed genes (DEGs), and hub genes were identified by different algorithms. A total of 350 DEGs were identified in bioinformatics data mining. Functional enrichment analysis showed that fibroblast growth factor 2(FGF2) and yes-associated protein 1(YAP1) protein levels were highly expressed in AD samples, indicating their potential regulatory roles in AD. Between October and November 2024, a total of 146 elderly individuals diagnosed with MCI and 54 healthy elderly subjects were successfully recruited. Enzyme linked immunosorbent assay (ELISA) was used to detect plasma hub gene protein concentration. The results showed that the expression levels of plasma FGF2 and YAP1 proteins in the MCI group were significantly higher compared to the control group. Logistic regression analysis indicated that high plasma FGF2 and YAP1 expression levels were independently associated with MCI in the elderly. The Area under the curve (AUC) of FGF2 model and YAP1 model were 0.907 and 0.972, respectively. Therefore, the high expression of plasma FGF2 and YAP1 proteins may be independent predictive risk factors for MCI in the elderly. Our findings may provide targets for the development of early minimally invasive, efficient, and convenient screening tools, and even for the treatment of AD in the future.

Objective: The triglyceride-glucose (TyG) index, combining fasting glucose and triglyceride levels, has emerged as a promising biomarker for coronary artery disease (CAD). However, evidence for its long-term prognostic value in CAD remains limited and inconclusive.Methods: This prospective cohort study was conducted at Beijing Hospital between January 2016 and December 2021, involving 23,591 patients with CAD. Based on the inclusion and exclusion criteria, a total of 11,325 CAD patients were included in the final analysis. TyG index was determined using the formula ln [fasting triglycerides (mg/dL) × fasting glucose. Eligible participants were stratified by TyG tertiles: Tertile 1 (TyG ≤ 8.39, n=3,775); Tertile 2 (8.40 ≤ TyG ≤ 8.92, n=3,776); Tertile 3 (TyG ≥ 8.93, n=3,774), with a median follow-up duration of 28 months. The primary outcomes were all-cause death and cardiovascular disease (CVD) death. The secondary outcome was major adverse cardiovascular events (MACE). Cox proportional hazards models and restricted cubic spline (RCS) analysis were applied to investigate the relationship between the TyG index and endpoints.Results: RCS analyses showed a monotonic increase in all-cause death, CVD death, and MACE risks with higher TyG. Kaplan-Meier curves confirmed worse survival in higher TyG tertiles. Multivariable-adjusted analysis revealed continuous TyG index was an independent risk factor for all-cause death (HR = 1.22; 95% CI 1.02-1.45) and CVD death (HR = 1.61; 95% CI 1.17-2.22). Using the lowest TyG index tertile as the reference (T1), the highest tertile (T3) group exhibited a 1.34-fold risk of all-cause death (95% CI 1.04-1.72), a 1.99-fold risk of CVD death (95% CI 1.23-3.21), and a 1.17-fold higher risk of MACE (95% CI 1.00-1.37), respectively. Subgroup analyses showed the continuous TyG index was significantly associated with the risk of all-cause death in acute coronary syndrome (ACS) (HR = 1.33, 95% CI 1.01-1.74) and CVD death in chronic coronary syndrome (CCS) (HR = 1.79, 95% CI 1.16-2.78). With T1 as the reference, patients with CCS in the T3 group had a 2.15-fold higher risk of CVD death (95% CI 1.10-4.23).Conclusion: The TyG index correlates with increased all-cause death, CVD death, and MACE risks in CAD, with prognostic value in both ACS and CCS, particularly in CCS. These findings establish TyG as a robust CAD biomarker, warranting further clinical research.