Abstract:Ferritinophagy is a selective autophagic process mediated by nuclear receptor coactivator 4 (NCOA4), which directs the degradation of the iron-storage protein ferritin to release bioavailable iron, thereby playing a pivotal role in the regulation of ferroptosis. Ferroptosis is a distinct form of programmed cell death characterized by its dependency on iron and driven by lipid peroxidation, and it has garnered growing attention in recent years within the field of cell death research. In the cardiovascular system, the coordinated regulation of ferritinophagy and ferroptosis is essential for maintaining iron homeostasis and cellular metabolic balance. However, dysregulation or sustained activation of this pathway may result in iron overload, oxidative stress, and lipid peroxidation, ultimately contributing to myocardial injury, atherosclerosis, and heart failure, thereby accelerating disease progression. Recent studies have highlighted the significant therapeutic potential of targeting the ferritinophagy/ferroptosis axis using iron chelators, antioxidants, and ferroptosis inhibitors in the treatment of cardiovascular diseases. This review provides a comprehensive overview of the molecular mechanisms underlying ferritinophagy and ferroptosis, elucidates their roles and crosstalk in the onset and progression of cardiovascular disorders, and critically evaluates emerging targeted therapeutic strategies. The aim is to offer a theoretical foundation and novel clinical insights for the precision management of cardiovascular diseases.

Abstract:Aim To investigate the mechanism by which high-salt intake upregulates transmembrane protein 16A (TMEM16A) and induces coronary artery remodeling in mice. Methods Thirty-six 8-week-old male C57BL/6J mice were randomly divided into three groups:control group (no additional NaCl in the diet), 10 g/L NaCl group (1 L of pure water contains 10 g of NaCl), and 20 g/L NaCl group (1 L of pure water contains 20 g of NaCl). Mice were fed for 8 weeks. Mouse body weight and systolic blood pressure (SBP) were measured weekly. After 8 weeks, serum was collected to measure serum Na＋ concentrations in mice; left ventricular mass index (LVMI) was measured to assess the effects of high-salt intake on the mouse heart; coronary flow (CF) was determined using the Langendorff retrograde constant-pressure perfusion method; HE staining was used to assess morphological changes in the coronary arteries, and calculate wall thickness (WT) percentage and wall area (WA) percentage. Microvascular tension recording instruments were employed to measure contractile changes in isolated coronary arteries from each group, standardizing coronary artery tension based on the area of the vascular ring. Western blot was used to detect TMEM16A protein expression in mouse coronary arteries. Dual immunofluorescence staining was used to detect TMEM16A and α-SMA expression in mouse coronary arteries. Results After 8 weeks, mice in the 10 g/L NaCl group and 20 g/L NaCl group showed a lower body weight change rate than control group, and SBP was significantly higher in both salt groups (P＜0.05 or P＜0.01). Compared with control mice, serum Na＋ concentration was increased in the 10 g/L NaCl group and 20 g/L NaCl group (P＜0.05 or P＜0.01). High-salt intake elevated LVMI and reduced CF, with the 20 g/L NaCl group exhibiting the most pronounced changes (P＜0.01). Percent wall thickness and percent wall area of coronary arteries were significantly greater in both salt groups (all P＜0.01). Contractile responses to 60 mmol/L KCl and 0.03 μmol/L endothelin-1 in coronary arteries were significantly enhanced in the 10 g/L and 20 g/L NaCl groups (P＜0.01). TMEM16A protein expression in coronary arteries was markedly up-regulated in the 20 g/L NaCl group (P＜0.01), and immunofluorescence revealed significantly increased TMEM16A and α-SMA signals in both salt groups (all P＜0.01). In addition, there was an obvious co-localization between TMEM16A and α-SMA. Conclusion High-salt intake causes coronary artery remodeling in mice, and its mechanism may be related to increasing TMEM16A expression.

Abstract:Aim To investigate the role and molecular mechanism of phosphofurin acidic cluster sorting protein-2 (PACS-2) in hypertension-related cardiac remodeling and dysfunction. Methods A mouse hypertension model was established by continuous infusion of angiotensinⅡ(AngⅡ), combined with PACS-2 knockout mice for group comparison.Systolic blood pressure (SBP) and echocardiography were used to evaluate cardiac function. Myocardial hypertrophy was assessed by heart weight/body weight ratio (HW/BW), heart weight/tibia length ratio (HW/TL), and cardiomyocyte cross-sectional area. Masson staining and immunohistochemistry staining were performed to assess myocardial fibrosis. Immunofluorescence was used to detect macrophage subsets, Western blot was used to detect myocardial fibrosis- and inflammation-related protein expression, and qPCR was used to measure inflammatory and fibrotic gene expression. In parallel, an in vitro AngⅡ-induced macrophage model combined with PACS-2 siRNA transfection was used to evaluate M1/M2 polarization and related functions. Results Compared with the control group, PACS-2 and the macrophage marker gene Mac-2 were significantly upregulated in the hypertension group, showing co-localization with Mac-2 (P＜0.05). SBP was elevated (P＜0.05), left ventricular ejection fraction (EF) and fractional shortening (FS) increased (P＜0.05), HW/BW, HW/TL and cardiomyocyte cross-sectional area were enlarged, and the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was increased (P＜0.05). Myocardial fibrosis analysis revealed significant collagen deposition and increased α-smooth muscle actin (α-SMA) expression, accompanied by elevated transforming growth factor-β (TGF-β) and p-Smad2 protein levels (P＜0.05). Inflammatory assessment showed an increase in M1 macrophages, upregulation of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) mRNA, and enhanced phosphorylation of IκB kinase α (IKKα) and p65 (P＜0.05), whereas M2 macrophage-related factors arginase 1 (Arg1), chitinase 3-like protein 3 (Ym1) and interleukin-10 (IL-10) remained unchanged. PACS-2 knockout significantly reduced SBP, EF, FS, myocardial hypertrophy and fibrosis indices, suppressed M1 polarization and pro-inflammatory cytokine secretion, and downregulated TGF-β/Smad and nuclear factor-κB (NF-κB) signaling (P＜0.05). In vitro, AngⅡ induced an increase in M1 macrophages and inflammatory cytokine expression, while PACS-2 knockout effectively inhibited these effects (P＜0.05) without significantly affecting M2 macrophage-related factors. Moreover, PACS-2 knockout reduced macrophage adhesion to and migration toward human umbilical vein endothelial cells (P＜0.05). Conclusions PACS-2 aggravates hypertension-related myocardial hypertrophy and fibrosis by promoting M1 macrophage polarization and inflammatory cytokine production and co-activating the TGF-β/Smad and NF-κB pathways. Inhibition of PACS-2 markedly attenuates cardiac remodeling and inflammatory responses, highlighting its potential as a therapeutic target.

Abstract:Aim To investigate the association between plasma remnant cholesterol (RC) level and coronary artery disease (CAD) in menopausal women and evaluate its clinical value. Methods In this retrospective study, 654 menopausal women who underwent coronary angiography at Changji Hui Autonomous Prefecture People's Hospital between January 2020 and December 2023 were included. Based on angiographic findings, participants were categorized into CAD group (n＝476) and non-CAD group (n＝178). Participants were stratified using the median RC level (0.37 mmol/L) as the cut-off value. Multivariable Logistic regression was used to assess the relationship between RC level and CAD, and ROC curves were generated to evaluate predictive performance. Subgroup analyses were conducted to test for interaction effects. Results RC levels were significantly higher in the CAD group compared with the non-CAD group (P＜0.001). After adjustment for conventional risk factors, high RC levels remain an independent risk factor for CAD (OR＝1.4,5%CI:1.081～3.285, P＝0.025). The individual AUC values of RC level, type 2 diabetes and hypertension were 0.6,0.572 and 0.602 respectively. When the three were analyzed together, the AUC value increased to 0.654 (95%CI:0.608～0.700, P＜0.001). A significant interaction was observed between RC level and lipoprotein(a) (≥300 mg/L) (P_for interaction＜0.05), with the highest CAD risk identified in the subgroup with high RC and high lipoprotein(a).Moreover, RC levels were significantly elevated in patients with low density lipoprotein cholesterol (LDLC)≥2.6 mmol/L and in those receiving statin therapy (both P＜0.05). Conclusions High RC levels are an independent risk factor for CAD in menopausal women and exhibit a synergistic effect with lipoprotein(a). Integrating RC level with type 2 diabetes and hypertension improves CAD risk prediction in this population, suggesting a potential strategy for refined risk stratification.

Abstract:Aim To investigate the relationship between stress hyperglycemia ratio (SHR) and left ventricular remodeling after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction. Methods A retrospective analysis was conducted on 1 160 patients with acute myocardial infarction who underwent PCI and had complete echocardiographic follow-up data in the Cardiology Department of Xuanwu Hospital, Capital Medical University from January 2016 to December 2023. The patients were divided into the remodeling group (n＝262) and the non-remodeling group (n＝898) according to the presence or absence of left ventricular remodeling, and the differences in SHR between the two groups were compared. Furthermore, the SHR were grouped into tertiles to analyze the relationship between different levels of SHR and left ventricular remodeling. Multivariable Logistic regression was used to analyze the independent correlation between SHR and left ventricular remodeling. Results The SHR was significantly higher in the remodeling group than that in the non-remodeling group (P＝0.023). Tertile analysis of SHR showed that the incidence of left ventricular remodeling in the high SHR group was significantly higher than that in the low SHR group (27.9% vs. 17.8%, P＝0.003). Multivariable Logistic regression analysis showed that SHR remained an independent risk factor for left ventricular remodeling after adjusting for confounders (OR＝1.3,5%CI:1.01～2.29, P＝0.043). ROC curve analysis showed that the area under the curve for predicting left ventricular remodeling in SHR was 0.57 (95%CI:0.52～0.63), with an optimal cutoff value of 0.88. Additionally, the performance of SHR remained stable across all subgroups. Conclusion SHR is positively correlated with the occurrence of left ventricular remodeling after PCI in patients with acute myocardial infarction, and is an independent risk factor for predicting left ventricular remodeling.

Abstract:Aim To explore the potential and independent risk factors associated with dyslipidemia in patients with obstructive sleep apnea syndrome (OSAS), and construct a predictive model for clinical use, with the goal of reducing the risk of dyslipidemia and subsequent cardiovascular events through early identification and intervention of modifiable factors. Methods A retrospective study was conducted on 181 patients diagnosed with OSAS who underwent polysomnography monitoring at the Second Hospital of Shanxi Medical University from January 2022 to March 2023. Among them, there were 76 patients with OSAS alone and 105 patients with OSAS complicated by dyslipidemia. General information, biochemical indicators, and polysomnography monitoring indicators of the patients were collected, and Spearman correlation analysis, univariate and multivariate Logistic regression models were used to analyze the independent risk factors of OSAS patients complicated with dyslipidemia. Results Compared with the OSAS alone group, the OSAS with dyslipidemia group had lower age, higher body mass index (BMI), monocyte count/high density lipoprotein cholesterol ratio (MHR), triglyceride/high density lipoprotein cholesterol ratio (TG/HDLC), low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio (LDLC/HDLC), and triglyceride glucose index (TyG) (P＜0.05), while high density lipoprotein cholesterol (HDLC) and non-rapid eye movement stage 2 sleep levels were significantly reduced. Spearman correlation analysis showed that triglyceride (TG) and TG/HDLC were positively correlated with the apnea hypopnea index (AHI) (r＝0.205, P＝0.006; r＝0.210, P＝0.005), while HDLC was negatively correlated with AHI (r＝－0.169, P＝0.024) and positively correlated with non-rapid eye movement stage 2 sleep (r＝0.156, P＝0.038). Multivariate logistic regression analysis showed that elevated TG/HDLC and MHR were independent risk factors and predictive indicators for OSAS complicated with dyslipidemia (P＜0.05). Conclusion High TG/HDLC and high MHR are independent risk factors and predictive indicators for OSAS complicated with dyslipidemia, with strong predictive value, and are of great significance for early prevention of coronary heart disease in OSAS patients.

Abstract:Aim To investigate the correlation between levels of three novel insulin resistance (IR) indicators including metabolic score for insulin resistance (METS-IR), estimated glucose disposal rate (eGDR), triglyceride-glucose index combined with body mass index (TyG-BMI), and the occurrence of coronary heart disease(CHD) in middle-aged population. Methods A total of 533 middle-aged individuals who were hospitalized in the Department of Cardiology of Liuzhou People's Hospital from January 2015 to December 2022 and underwent coronary angiography were enrolled as the research subjects. They were divided into CHD group (241 cases) and control group (292 cases) according to the results of coronary angiography. The general data and laboratory examination indicators of the subjects were collected, and METS-IR, eGDR, TyG-BMI were calculated using relevant formulas. Bivariate Spearman correlation, multivariate Logistic regression, and restricted cubic spline plots were used to analyze the correlation between levels of various IR indicators and the occurrence of CHD in middle-aged population. Subgroup analysis and interaction tests were conducted to examine differences in the main results among different people. Receiver operating characteristic (ROC) curve was used to evaluate the value of various IR indicators in predicting the occurrence of CHD in middle-aged population. ResultsMETS-IR, TyG-BMI were higher in CHD group than those in control group, while eGDR was lower than that in control group (P＜0.05). The Spearman correlation analysis results showed positive correlations between METS-IR, TyG-BMI and CHD (r＝0.312 and 0.267, respectively; all P＜0.001), and negative correlation between eGDR and CHD in middle-aged population (r＝－0.275, P＜0.001). Multivariate Logistic regression analysis showed that whether as continuous or categorical variable, METS-IR, eGDR, TyG-BMI were independent influencing factors for CHD in middle-aged population (P＜0.001). Compared with the lowest quartile group, the risk of CHD in 2nd, 3rd, and 4th quartile groups of METS-IR increased by 2.286-fold (OR:3.6,5%CI:1.823~5.924), 2.061-fold (OR:3.1,5%CI:1.670~5.609), and 4.646-fold (OR:5.6,5%CI:3.018~10.563) respectively; the risk of CHD in 4th quartile group of eGDR decreased 79.2% (OR:0.8,5%CI:0.114~0.379); the risk of CHD in 2nd, 3rd, and 4th quartile groups of TyG-BMI increased by 1.579-fold (OR:2.9,5%CI:1.438~4.625), 2.155-fold (OR:3.5,5%CI:1.761~5.655), and 3.142-fold (OR:4.2,5%CI:2.317~7.407) respectively. The restricted cubic spline plots revealed that, after adjusting for confounding factors, METS-IR, TyG-BMI levels were positively nonlinearly correlated with CHD (P for overall＜0.001, P for nonlinearity＝0.002 and 0.043, respectively), while eGDR level was negatively nonlinearly correlated with CHD (P for overall＜0.001, P for nonlinearity＝0.010). Subgroup analysis showed that the association between various IR indicators and CHD were basically consistent in population other than those with overweight/obesity, diabetes and hypertension. ROC curve analysis showed that the areas under the curve (AUC) of METS-IR, eGDR, TyG-BMI combined with clinical factors in predicting CHD were 0.746 (95%CI:0.704～0.788, P＜0.001), 0.750(95%CI:0.709～0.792, P＜0.001) and 0.742 (95%CI:0.700～0.784, P＜0.001) respectively. Conclusion The levels of METS-IR, eGDR, and TyG-BMI are independently associated with the occurrence of CHD in middle-aged population. All three indicators have certain predictive value for CHD and can serve as relatively ideal indicators for predicting CHD.

Abstract:Aim To explore the association between aspartate transaminase (AST)/alanine transaminase (ALT) ratio (De Ritis ratio) and 28-day mortality in patients with ischemic heart disease, and to analyze its specific predictive value in populations with different comorbidities. Methods A retrospective study was conducted, and 7 513 patients with ischemic heart disease were finally included after screening for missing values, and all data were obtained from MIMIC-IV database. Extracting based on the ICD codes for ischemic heart disease, mean imputation was used for missing time-related and laboratoriy data. Variables with a missing rate exceeding 20% were excluded from the model. The De Ritis ratio was assessed using a multivariate Cox model with restricted cubic splines with four knots and adjusted for SOFA score, APACHEⅡ score, organ support, and biomarkers. LASSO regression was used for variable selection. Model performance was evaluated by the ROC-AUC (DeLong method) and calibration metrics. Prespecified subgroup analysis were performed to explore the modifying effect of comorbidities on the association between the De Ritis ratio and mortality. Results The De Ritis ratio was significantly associated with the 28-day mortality in patients with ischemic heart disease.Kaplan-Meier survival analysis showed that the Q4 group with the highest De Ritis ratio had a significantly higher 28-day mortality compared to the Q1 group (20.52% vs. 15.08%, P＜0.0001). Univariate Cox regression analysis showed that the risk of death increased significantly with the increase of De Ritis ratio, the risk of death was 42.1% higher in Q4 group than that in Q1 group (P＜0.001). Multivariate Cox regression analysis showed that age, respiratory rate, and sepsis status were identified as independent risk factors, and the AUC value of the model was 0.821. The decision curve analysis showed that the De Ritis ratio had a net clinical benefit within the threshold probability range of 25%～75%. The restrictive cubic spline regression model showed that there was no significant nonlinear relationship between the De Ritis ratio and mortality after adjusting for confounding factors (P＝0.143). Subgroup analysis showed that age, cirrhosis, and mechanical ventilation had significant interactions between the association between this ratio and the risk of death (P＜0.05), and the predictive value was more pronounced in young patients, non-mechanically ventilated patients and those with severe inflammatory. The risk increase in the young group was 24% higher than in the elderly group; in non-mechanically ventitated patients, the De Ritis ratio was strongly associated with mortality risk. In patients receiving mechanical ventilation, no significant correlation was observed (P＝0.213). Conclusion The De Ritis ratio is significantly positively correlated with the 28-day mortality of patients with ischemic heart disease, and therefore can be used as a warning indicator to evaluate the short-term mortality risk of such patients.

Abstract:Coronary heart disease (CHD) is a major global public health issue that poses a serious threat to human health. Despite advances in treatment improving the prognosis for some patients, hospital mortality rates remain largely unchanged, and significant disparities in treatment outcomes persist across regions and medical institutions. Accurate risk prediction models play a critical role in identifying high-risk populations, formulating personalized intervention strategies, and improving patient outcomes. Over the past 30 years, more than a dozen CHD prognosis prediction models have been developed worldwide. These models differ significantly in terms of target populations, predicted outcomes, selected predictors, and follow-up durations, posing various limitations and requirements for clinical application. This article systematically reviews CHD prognosis prediction models developed globally, analyzes their characteristics in terms of algorithm design, data processing, and clinical application. It also focuses on optimizing data integration methods, enhancing model interpretability, and improving cross-population validation strategies. The aim is to provide a scientific basis for precise prevention and management of CHD, offer robust support for clinical decision-making and public health management, and serve as a valuable reference for the development of medical models driven by multi-modal data.

Abstract:Atherosclerosis (As) is a common disease in the cardiovascular system, characterized by the formation of atherosclerotic plaques or fibrous plaques in the vascular intima, leading to vessel wall hardening, lumen stenosis, and reduced elasticity, thereby causing ischemic changes in corresponding organs. Kaempferol is a natural flavonoid compound found in various plants and fruits, possessing significant anti-inflammatory and antioxidant properties. Due to the limitations of traditional lipid-lowering therapies, natural products with anti-As activity and potential benefits for human health have garnered increasing attention in recent years. The molecular mechanisms of kaempferol in combating As have been confirmed. Based on the latest research advances domestically and internationally, this article systematically reviews the anti-inflammatory, antioxidant, and anti-As effects of kaempferol, elucidates its potential mechanisms of action, and aims to provide theoretical references for the prevention and treatment of As.

Abstract:Exosomes (Exo) are small vesicles secreted by various cells and encapsulated by lipid bilayer membranes, which are widely involved in intercellular information communication, and can carry diverse bioactive molecules derived from donor cells, especially microRNA (miRNA). In recent years, the functions and potential mechanisms of exosomal miRNAs in the occurrence and development of atherosclerosis (As) have received extensive attention and in-depth study. This review summarizes the roles of exosomal miRNAs in As, focusing on their cellular sources and regulatory effects on the function of recipient cells. Meanwhile, this review also discusses their potential application value and prospect in the diagnosis and therapy of As.