Chronic stress refers to the non-specific systemic reaction that occurs when the body is stimulated by various internal and external negative factors over a long time. The physiological response to chronic stress exposure has long been recognized as a potent modulator in the occurrence of atherosclerosis. Furthermore, research has confirmed the correlation between atherosclerosis and cardiovascular events. Chronic stress is pervasive during negative life events and may lead to the formation of plaque. Several epidemiological studies have shown that chronic stress is an independent risk factor for the development of vascular disease and for increased morbidity and mortality in patients with pre-existing coronary artery disease. One possible mechanism for this process is that chronic stress causes endothelial injury, directly activating macrophages, promoting foam cell formation and generating the formation of atherosclerotic plaque. This mechanism involves numerous variables, including inflammation, signal pathways, lipid metabolism and endothelial function. The mechanism of chronic stress in atherosclerosis should be further investigated to provide a theoretical basis for efforts to eliminate the effect of chronic stress on the cardiocerebral vascular system.

Myocardial infarction (MI) has been considered as the leading cause of cardiovascular-related deaths worldwide. Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factor family that promotes angiogenesis after MI; however, it has poor clinical efficacy due to proteolytic degradation, low drug accumulation, and severe drug-induced side effects. In this study, an injectable disulfide-cross-linked chitosan hydrogel loaded with bFGF was prepared via a thiol–disulfide exchange reaction for MI treatment. The thiol–disulfide exchange reaction between pyridyl disulfide-modified carboxymethyl chitosan (CMCS-S-S-Py) and reduced BSA (rBSA) was carried out under physiological conditions (37 °C and pH 7.4). The mechanical properties of the disulfide-cross-linked chitosan hydrogel were evaluated based on the molar ratio of the pyridyl disulfide groups of CMCS-S-S-Py and the thiol groups of rBSA. The disulfide-cross-linked chitosan hydrogel showed good swelling performance, rapid glutathione-triggered degradation behavior and well-defined cell proliferation towards NIH 3T3 fibroblast cells. In the process of establishing a rat MI model, the squeezing heart method was used to make the operation more accurate and the mortality of rats was decreased by using a ventilator. The disulfide-cross-linked chitosan hydrogel loaded with bFGF (bFGF-hydrogel) was injected into a peri-infarcted area of cardiac tissue immediately following MI. Echocardiography demonstrated that the left ventricular functions were improved by the bFGF-hydrogel after 28 days of treatment. Histological results revealed that the hydrogel significantly reduced the fibrotic area of MI, and this was further improved by the bFGF-hydrogel treatment. TUNEL and immunohistochemical staining results showed that the bFGF-hydrogel had a more synergistic effect on antiapoptosis and proangiogenesis than using either bFGF or the hydrogel alone.

Background: Vascular calcification is related to many diseases. Iron has a certain relationship with endothelial cells and vascular calcification. The purpose of this study was to assess the effect of iron overload on endothelial cell calcification and related mechanisms through cell experiments. Methods: Human umbilical vein endothelial cells were treated with different concentrations of FeSO₄ (50, 100, 150, and 200 µM), and deferoxamine (DFO) and ferrostatin. Alkaline phosphatase activity, malondialdehyde (MDA) level, reactive oxygen species (ROS) level, and lipid superoxidation after FeSO₄ treatment were assessed. Alizarin red staining was used to observe calcium deposition. Quantitative polymerase chain reaction (qPCR) and western blot were adopted to examine the expression of calcification markers, iron metabolism-related factors, apoptosis pathway-related factors and ferroptosis markers. The TUNEL method was employed to detect cell apoptosis. Results: FeSO₄ of 100 µM significantly promoted the occurrence of cell ferroptosis, increased the levels of MDA and ROS, and decreased the ratio of glutathione (GSH) or glutathione disulfide (GSSG) and the expression level of glutathione peroxidase (GPX4). The addition of DFO and ferrostatin significantly modified the effects of FeSO₄. Calcium deposition was most obvious in the cells treated with 100 µM FeSO₄. FeSO₄ significantly upregulated Runt-related transcription factor 2 (RUNX2) and Bone morphogenetic protein 2 (BMP2), ferritin heavy chain (FTH) and ferritin light chain (FTL), and downregulated Matrix Gla Protein (MGP) and divalent metal transporter 1 (DMT1). The results also showed that FeSO₄ induced cell apoptosis by TUNEL method. The elevated Bcl2-associated death protein (Bad) and Bcl2-associated X protein (Bax) and the reduction in Bcl-2, p-Bad, p-AKT, and t-AKT were found. DFO and ferrostatin significantly reduced the iron-induced calcification and apoptosis of endothelial cells. DFO significantly increased the expression level of Bcl-2, and reduced the expression level of Bad. Conclusions: Iron overload contributes to the process of endothelial cell calcification by inducing apoptosis and ferroptosis. Iron chelators and ferroptosis inhibitors alleviate endothelial cell apoptosis, ferroptosis, and calcification induced by iron overload.

Background: This study aimed to define changes in the metabolic and protein profiles of patients with calcific aortic valve disease (CAVD).Methods and results: We analyzed cardiac valve samples of patients with and without (control) CAVD (n = 24 per group) using untargeted metabolomics and tandem mass tag-based quantitative proteomics. Significantly different metabolites and proteins between the CAVD and control groups were screened; then, functional enrichment was analyzed. We analyzed co-expressed differential metabolites and proteins, and constructed a metabolite-protein-pathway network. The expression of key proteins was validated using western blotting. Differential analysis identified 229 metabolites in CAVD among which, 2-aminophenol, hydroxykynurenine, erythritol, carnosine, and choline were the top five. Proteomic analysis identified 549 differentially expressed proteins in CAVD, most of which were localized in the nuclear, cytoplasmic, extracellular, and plasma membranes. Levels of selenium binding protein 1 (SELENBP1) positively correlated with multiple metabolites. Adenosine triphosphate-binding cassette transporters, starch and sucrose metabolism, hypoxia-inducible factor 1 (HIF-1) signaling, and purine metabolism were key pathways in the network. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), calcium²⁺/calmodulin-dependent protein kinase II delta (CAMK2D), and ATP binding cassette subfamily a member 8 (ABCA8) were identified as hub proteins in the metabolite-protein-pathway network as they interacted with ADP, glucose 6-phosphate, choline, and other proteins. Western blotting confirmed that ENPP1 was upregulated, whereas ABCA8 and CAMK2D were downregulated in CAVD samples.Conclusion: The metabolic and protein profiles of cardiac valves from patients with CAVD significantly changed. The present findings provide a holistic view of the molecular mechanisms underlying CAVD that may lead to the development of novel diagnostic biomarkers and therapeutic targets to treat CAVD.

Background: Acute coronary syndrome (ACS) is the most time-sensitive acute cardiac event that requires rapid dispatching and response. The medical priority dispatch system (MPDS), one of the most extensively used types of emergency dispatch systems, is hypothesized to provide better-quality prehospital emergency treatment. However, few studies have revealed the impact of MPDS use on the process of ACS care. Objective: This study aimed to investigate whether the use of MPDS was associated with higher prehospital diagnosis accuracy and shorter prehospital delay for patients with ACS transferred by an emergency medical service (EMS), using a national database in China. Methods: This retrospective analysis was based on an integrated database of China’s MPDS and hospital registry. From January 1, 2016, to December 31, 2020, EMS-treated ACS cases were divided into before MPDS and after MPDS groups in accordance with the MPDS launch time at each EMS center. The primary outcomes included diagnosis consistency between hospital admission and discharge, and prehospital delay. Multivariable logistic regression and propensity score–matching analysis were performed to compare outcomes between the 2 groups for total ACS and subtypes. Results: A total of 9806 ACS cases (3561 before MPDS and 6245 after MPDS) treated by 43 EMS centers were included. The overall diagnosis consistency of the after MPDS group (Cohen κ=0.918, P<.001) was higher than that of the before MPDS group (Cohen κ=0.889, P<.001). After the use of the MPDS, the call-to-EMS arrival time was shortened in the matched ACS cases (20.0 vs 16.0 min, P<.001; adjusted difference: –1.67, 95% CI –2.33 to –1.02; P<.001) and in the subtype of ST-elevation myocardial infarction (adjusted difference: –3.81, 95% CI –4.63 to –2.98, P<.001), while the EMS arrival-to-door time (20.0 vs 20.0 min, P=.31) was not significantly different in all ACS cases and subtypes. Conclusions: The optimized use of MPDS in China was associated with increased diagnosis consistency and a reduced call-to-EMS arrival time among EMS-treated patients with ACS. An emergency medical dispatch system should be designed specifically to fit into different prehospital modes in the EMS system on a regional basis.

Background: Bicuspid aortic valve (BAV) is common congenital malformation, bicuspid aortic stenosis accounts for a substantial proportion of patients with aortic valve stenosis (AS). Bicuspid AS are more likely to have aortic dilatation with slightly less elliptical annuli, which might lead to paravalvular aortic valve regurgitation (AR) and permanent pacemaker implantation (PPM) after TAVI with higher mortality. Our study aims to understand the therapeutic efficacy and safety of transcatheter aortic valve implantation (TAVI) with a supra-annular structure-based sizing strategy in Chinese AS patients with BAV versus tricuspid aortic valve (TAV). Methods: Seventy-four consecutive tricuspid AS patients and 44 bicuspid AS patients were included and enrolled in the study for analysis. Both groups underwent TAVI performed using balloon sizing less than mild paravalvular AR to assess the proper prosthesis size. The myocardial function within 1 year postoperative were sequentially evaluated using the New York Heart Association (NYHA) class, and echocardiography measurements. The incidence rates of complications at 30 days and 1 year were analyzed. During the 1-year follow-up, the time of death from any cause or complications in both groups was recorded. Results: The study found that the percentage of patients with class III–IV of NYHA dropped after TAVI in both groups, and no significant difference between both groups at 1 year. Compared with the tricuspid AS group patients, Bicuspid group patients had more improvement in mean aortic valve gradient from baseline to 1year (−47.47±13.38 vs. −50.22±19.25 mmHg, P<0.05). There were no significant differences in 30-day and one-year compliance outcomes except a lower incidence of AR at post-procedure and 30 days in the tricuspid AS group as the Bicuspid AS group. There were no statistically significant differences in the time of death from any cause or significant complications between groups. Conclusions: TAVI has acceptable therapeutic efficacy and safety and is feasible for AS patients with BAV in China.