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: Heart failure with preserved ejection fraction (HFpEF) is a systemic syndrome primarily associated with fibrosis, oxidative stress, inflammation, and cellular apoptosis. Growth differentiation factor 15 (GDF15), a biomarker commonly used in clinical studies, exhibits protective effects on the myocardium. Therefore, the focus of the present study is to determine the mechanism by which GDF15 protects cardiac function in HFpEF. Methods: We conducted functional enrichment analysis and protein-protein interaction network analysis on genes highly expressed in HFpEF but lowly expressed in normal samples. We established an HFpEF rat model by feeding the rats with a high-fat diet and administering N-omega-nitro-l-arginine-methyl ester (L-NAME) in their drinking water and silenced GDF15 by tail vein injection of lentivirus (L3110). After 12 weeks of feeding, echocardiographic examinations were performed. Following euthanasia of the rats, blood and heart tissue samples were collected. Heart tissue sections were stained using Masson’s trichrome and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining methods. Western blot (WB) analysis was employed to determine the concentrations of relevant proteins. Results: The echocardiographic results showed that compared with the HFpEF + MOCK group, the HFpEF+silencing GDF15 (siGDF15) group exhibited more severe cardiac dysfunction, with significant decreases in ejection fraction (p < 0.05) and E/A ratio (p < 0.001). WB results demonstrated that, compared with the HFpEF + MOCK group, the HFpEF+siGDF15 group exhibited increased expression of cardiac fibrosis-associated proteins, including collagen I (p < 0.01), collagen III (p < 0.01), and α-smooth muscle actin (α-SMA) (p < 0.01). Additionally, oxidative stress-associated biomarkers such as myeloperoxidase (MPO) (p < 0.01) and oxidized low-density lipoprotein (ox-LDL) (p < 0.01), inflammation-associated biomarkers, including interleukin-1 beta (IL-1β) (p < 0.01), interleukin-6 (IL-6) (p < 0.01), interleukin-8 (IL-8) (p < 0.01), and tumor necrosis factor α (TNFα) (p < 0.01), and apoptosis-associated biomarkers like cleaved caspase-3 (p < 0.01) and BCL2-associated X (BAX) (p < 0.01) were also upregulated in HFpEF+siGDF15 group. Conclusions: Our research indicates that GDF15 preserves cardiac function by inhibiting myocardial fibrosis, reducing myocardial cell oxidative stress, alleviating cardiac inflammation, and suppressing myocardial cell apoptosis.

BACKGROUND:Two-dimensional speckle tracking echocardiography (2D-STE) is a novel and non-invasive technique for the diagnosis of coronary artery disease (CAD). This retrospective study from a single center aimed to identify myocardial ischemia using 2D-STE in CAD patients identified by angiography. MATERIAL AND METHODS:From March 1 to November 30, 2019, 690 patients in Beijing Hospital were enrolled. After angiography, 346 patients were diagnosed with CAD. Reduction in vessel diameter of ≥50% by stenosis in at least 1 major coronary artery or its main branch was considered CAD. Analysis of 2D-STE was performed using EchoPAC version 201. RESULTS:The global strain was significantly impaired in CAD patients (P<0.01). Global longitudinal peak strain (GLPS) was analyzed in layers. For GLPS of the epicardium, the odds ratio (OR) was 1.297 (1.217-1.382; P=0.002), the area under the curve (AUC) was 0.727, and the cut-off value was -16.95; sensitivity and specificity were 73.7% and 63.0%, respectively. For GLPS of the middle layer, the OR was 1.260 (1.192-1.333; P<0.001), the AUC was 0.732, and the cut-off value was -20.95; sensitivity and specificity were 82.4% and 56.2%, respectively. For GLPS of the endocardium, the OR was 1.193 (1.137-1.251; P<0.001), the AUC was 0.708, and the cut-off value was -22.95; sensitivity and specificity were 82.9% and 52.9%, respectively. CONCLUSIONS:The findings from this study support the clinical application of 2D-STE in patient populations with suspected myocardial ischemia due to CAD. Therefore, 2D-STE combined with ECG monitoring may have a future role for early screening of CAD patients.

Background: The atherogenic index of plasma (AIP), calculated from triglyceride and high-density lipoprotein cholesterol levels, is associated with atherosclerosis and coronary artery disease (CAD). However, evidence concerning the impact of the AIP on CAD severity remains limited. This study aims to assess the correlation between AIP and the severity of CAD. Methods: This study included 19,929 hospitalized participants diagnosed with CAD. After excluding participants with missing data, aged >75 years, or diagnosed with chronic kidney disease or cancer, a total of 2561 individuals were included. The 2561 participants were divided into three AIP tertile groups: AIP1 (AIP <0.016, n = 854), AIP2 (0.016 ≤ AIP < 0.216, n = 853), and AIP3 (AIP ≥0.216, n = 854). In this study, CAD severity was determined by the count of coronary arteries exhibiting stenosis of 50% or greater. Multivessel CAD was defined as ≥50% stenosis in two or more major coronary arteries. The relationship between AIP and CAD severity was assessed using logistic regression models. Results: Results indicate that the AIP independently predicts CAD severity, with an odds ratio of 1.700 (95% confidence interval (CI): 1.160–2.491; p = 0.007). The AIP3 group demonstrated a significantly higher risk of multivessel CAD compared to the AIP1 group (odds ratio (OR), 1.441; 95% CI: 1.124–1.848; p = 0.004), particularly in patients without diabetes mellitus (OR, 1.421; 95% CI: 1.030–1.962; p = 0.033). Conclusions: The AIP was significantly associated with CAD severity, suggesting that it could be a convenient and valuable marker for severity stratification in patients with CAD in clinical practice.

Objective: Heart failure is a complex end stage result of various cardiovascular diseases, and has a poor prognosis. Exercise training according to oxidative stress, myocardial fibrosis, inflammation pathways improve cardiac function. The aim of this study was to investigate the possible protective effects of exercise training against cardiac damage in doxorubicin (DOX)-induced heart failure in Sprague-Dawley Rats. Design and method: This study used 45 male Sprague-Dawley (SD) rats weighing 150 ± 20 g that were randomly divided into a control group (normal saline), doxorubicin (DOX) group and DOX plus exercise (DOX + E) group. Heart failure was induced experimentally by intraperitoneal injections of the cardiotoxic agent DOX. All groups received different treatment for 8 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes; the blood samples were stored at minus 80°C until use. Heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The heart was stored in liquid nitrogen for immunoblotting or mRNA analysis. Results: Left ventricular fractional shortening and ejection fraction were higher in DOX + E group rats than in DOX group rats on an echocardiographic examination (Figure 1 and Table 1). Significant cardiac tissue damage (haematoxylin and eosin, Masson's trichrome staining) was seen in rats of the DOX group compared to those of the DOX + E group (Figure2). Exercise inhibited DOX-induced cardiac fibrosis (transforming growth factor, smooth muscle actin, collagen I, and collagen III) and oxidative stress (Nox4, p53) in an immunoblotting analysis (Figure 3 and 4). Conclusions: These results indicate that exercise training may be a potential therapeutic target for cardiac damage caused by DOX-induced heart failure.