One important pathogenic process that contributes to subsequent damage after myocardial infarction (MI) revascularization is myocardial ischemia/reperfusion injury (MI/RI). Its underlying mechanisms are controlled by traditional post-translational modifications (PTMs) like acetylation, methylation, phosphorylation, and ubiquitination, and involve several cell death pathways, such as autophagy, apoptosis, pyroptosis, and ferroptosis. Histone lysine lactylation (Kla), a novel metabolically related epigenetic regulation mechanism, has attracted a lot of attention in recent years. This review systematically clarifies the crucial role of lactate in cardiac energy metabolism and its influence on Kla modification, exploring Kla's dual regulatory function in MI/RI. It demonstrates a significant interaction between Kla and changes like acetylation, phosphorylation, N6-methyladenosine (m6A) methylation, and ubiquitination, thereby establishing putative connections that regulate cell death in MI/RI. Targeting lactate-related molecules such as lactate dehydrogenase A (LDHA), monocarboxylate transporters (MCTs), and histone deacetylases (HDACs) shows therapeutic potential. Therefore, targeted intervention molecules applicable at different stages of MI/RI are explored. Ultimately, elucidating the dynamic patterns of Kla and its crucial involvement in various biological processes will create new paradigms and potential therapeutic targets for the prevention and treatment of MI/RI.

The contribution of socioeconomic position (SEP) to arrhythmias remains unclear. We aimed to examine the extent to which accelerated ageing mediates the associations of SEP and atrial fibrillation/flutter (AF), ventricular arrhythmias (VA), and bradyarrhythmias. Data were collected from the UK Biobank. SEP was determined by household income, education level and employment status using latent class analysis. Accelerated ageing was assessed by PhenoAge and BioAge acceleration calculated using nine and seven blood biomarkers respectively. Outcomes were AF, VA and bradyarrhythmia. Counterfactual mediation analysis was used to evaluate the mediation proportion of accelerated ageing in the association of SEP with arrhythmias. A total of 224,389 participants were included in the study. With a median follow-up of 13.33 years, 1,843 (0.82

Background: The role of biological aging in the progression of atrial fibrillation (AF) remains unclear. Therefore, the present study aimed to investigate the influence of biological aging markers on transitions from health to AF, complications, and death.Methods: Two UK Biobank datasets were analyzed: 260,198 participants for the Klemera-Doubal method for biological age (KDM-BA) and PhenoAge analyses, and 339,603 for telomere length analyses, excluding those with AF, complications (heart failure, myocardial infarction, cerebral infarction, dementia, and arterial embolic diseases) at baseline. The present study employed a multi-state model to evaluate the associations between biological aging markers and the progression of AF. Mediation analyses were utilized to assess the role of systemic inflammation.Results: During the follow-up period, 9.51-9.67% of patients in the two datasets developed AF, among whom 17.59-17.85% progressed to complications, with 8.20-10.83% of these patients dying from AF-related complications. In comparison with Q1, Q4 of the KDM-BA and PhenoAge analyses was associated with elevated risks across transitions, particularly from baseline to AF (hazard ratios (HR): 1.09, 95% confidence interval (CI): 1.04-1.14; HR: 1.30, 95% CI: 1.25-1.35), baseline to death (HR: 1.10, 95% CI: 1.04-1.16; HR: 1.11, 95% CI: 1.06-1.16), and AF to complication (HR: 1.75, 95% CI: 1.58-1.94; HR: 1.52, 95% CI: 1.37-1.68). Moreover, Q4 of the telomere length analyses showed protective effects against AF onset (HR: 0.83, 95% CI: 0.80-0.86), progression to complications (HR: 0.78, 95% CI: 0.72-0.84), and from baseline to death (HR: 0.91, 95% CI: 0.88-0.94). Systemic inflammation was associated with up to 29.95% of these associations.Conclusions: Associations were found between biological aging markers (higher KDM-BA and PhenoAge, and shorter telomere length) and the risk of AF transitions, particularly with respect to an increased risk of AF and progression to complications. These findings underscore the importance of biological age in AF risk stratification and prevention.

Impairment in cholesterol uptake and efflux is the main reason contributing to foam cell formation, which is a marker and key step in the atherosclerotic process. Overexpression of long intergenic non-coding RNA-p21 (lincRNA-p21) was reported to alleviate the development of atherosclerosis. However, whether lincRNA-p21 exerts an antiatherogenic function by alleviating lipid metabolism dysfunction and foam cell formation remains unknown. In our study, human THP-1 monocytes were stimulated for 48 h by phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and THP-1-derived macrophages were further treated for 24 h with oxidized low-density lipoprotein (ox-LDL) to differentiate into foam cells. THP‑1 macrophage-derived foam cells were transfected with si-NC/si-lincRNA-p21 or LV-NC/LV-lincRNA-p21 for 48 h to knock down or overexpress lincRNA-p21. lincRNA-p21 expression was reduced in THP-1-derived macrophages after ox-LDL treatment. lincRNA-p21 knockdown promoted lipid uptake and accumulation and inhibited cholesterol efflux in ox-LDL-treated THP-1 macrophages, while lincRNA-p21 overexpression exerted an opposite effect on cholesterol influx and efflux. Importantly, lincRNA-p21 attenuated cholesterol influx by suppressing the PKCδ/Akt/Erk/SR-A/CD36 pathway and enhanced cholesterol efflux by promoting the PPARγ/LXRα/ABCA1/ABCG1 pathway in foam cells derived from THP-1 macrophages.

Myocardial ischemia-reperfusion injury is a significant complication of reperfusion therapy and a primary cause of mortality in patients with acute myocardial infarction. The pathogenic mechanism involved in myocardial ischemia-reperfusion injury is intricate, and effective preventive and therapeutic strategies remain limited in clinical practice. Recently, pyroptosis has emerged as a novel regulatory form of cell death and has attracted widespread attention as a key focus in the study of disease mechanisms and therapeutic targets. Studies indicate a close association between pyroptosis and the pathophysiological processes underlying myocardial ischemia-reperfusion injury. This article provides a comprehensive review of recent advances in research on pyroptosis in the context of myocardial ischemia-reperfusion injury. Therefore, this review aims to offer new insights into the prevention and treatment of myocardial ischemia-reperfusion injury while minimizing redundancy in the existing literature.

BACKGROUND:Ambient air pollution is associated with heart failure (HF), but underlying biological mechanisms remain unclear. We aimed to elucidate metabolic pathways linking air pollution exposure with HF. METHODS:This prospective cohort study analysed 229 812 UK Biobank participants with nuclear magnetic resonance metabolomics data. Air pollution score was constructed by fine particulate matter, coarse particulate matter, nitrogen dioxide and nitrogen oxides. Air pollution-associated metabolic signatures were identified using elastic net regression among 251 circulating metabolites. Cox regression evaluated associations between metabolic signatures and incident HF risk. Mediation analysis quantified metabolic signatures' role in air pollution-HF relationships. RESULTS:During median 13.1-year follow-up, 8986 participants (3.9%) developed HF. We identified 53 metabolic metabolites reflecting air pollution exposure, comprising lipoprotein metabolism markers (22.6%), fatty acids (17.0%) and amino acids (13.2%), which were used to construct the air pollution-related metabolic signatures score. After adjustment for confounding factors, each SD increase in the metabolic signatures was associated with 8% elevated HF risk (HR 1.08, 95% CI 1.06 to 1.11). Participants in the highest quantile showed a 24% increased HF risk compared with those in the lowest quantile (HR 1.24, 95% CI 1.16 to 1.3). The metabolic signatures mediated 13.08% (95% CI 12.15% to 15.71%) of air pollution-HF associations, with lipoprotein metabolism and fatty acid signatures as primary mediators. CONCLUSIONS:Air pollution was associated with increased HF risk, with metabolic perturbations appearing to play a mediating role. These metabolic signatures provide insights into potential mechanisms linking air pollution to cardiovascular outcomes.

ABSTRACT:The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms. Testosterone, as one of the most critical sex hormones, is essential for the development of the reproductive system, maintenance of reproductive function, and the overall health of males. The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes. Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis. We also examined the specific effects of these genes on the occurrence, development, and treatment of common male diseases, including late-onset hypogonadism, erectile dysfunction, male infertility, and prostate cancer.

We aimed to explore the association between plant-based dietary (PBD) patterns and obesity trajectories in middle-aged and elderly, as well as obesity trajectories linked to cardiovascular disease (CVD) risk. A total of 7108 middle-aged and elderly UK Biobank participants with at least three physical measurements were included. Dietary information collected at enrolment was used to calculate the healthful plant-based diet index (hPDI). Group-based trajectory modeling identified two trajectories for each adiposity measure: BMI Low-Smooth and High-Growth-Decline; FMI Low-Smooth and High-Growth-Decline; WHR Low-Growth and High-Growth. Logistic regression showed that participants in the medium and high hPDI groups were less likely to follow the BMI High-Growth-Decline (OR = 0.72, 95% CI: 0.60-0.87; OR = 0.49, 95% CI: 0.39-0.61), FMI High-Growth-Decline (OR = 0.71, 95% CI: 0.60-0.84; OR = 0.55, 95% CI: 0.46-0.66), and WHR High-Growth (OR = 0.73, 95% CI: 0.61-0.87; OR = 0.52, 95% CI: 0.43-0.63) trajectories. After a median follow-up time of 3.88 years, Cox regression showed higher CVD risk for participants in these trajectories (HR = 1.70, 95% CI: 1.37-2.11; HR = 1.68, 95% CI: 1.37-2.06; HR = 1.30, 95% CI: 1.04-1.63). A healthy PBD pattern was associated with the maintenance of a healthy BMI classification. Furthermore, the long-term stabilization of a healthy BMI classification may be linked to a reduced risk of CVD.

Background Myocardial ischemia-reperfusion injury (MIRI) drives adverse cardiac remodeling and ventricular dysfunction, posing a major therapeutic challenge and substantially contributing to global mortality. Despite therapeutic advances, effective MIRI treatments remain limited. Ginsenoside Rd (GSRd), a bioactive constituent from traditional Chinese herbs, has been widely recognized to have cardioprotective effects. However, the role of GSRd in MIRI remains unclear. Purpose To elucidate the therapeutic efficacy and the underlying molecular mechanisms of GSRd against MIRI. Methods A MIRI model was established in male C57BL/6J mice via left anterior descending coronary artery (LAD) ligation followed by reperfusion. Post-surgery, mice received daily intraperitoneal injections of vehicle, dapagliflozin (1 mg/kg), or GSRd (5, 10, 20 mg/kg) for 28 days. Cardiac function was evaluated by echocardiography. Histopathological changes were assessed using hematoxylin and eosin (H&E), Masson’s trichrome, TUNEL, and immunofluorescence staining. In vitro, isolated adult mouse CMs were subjected to H/R injury and GSRd-containing serum treatment to assess proliferation. Cardiomyocyte proliferation was assessed by Ki-67 immunofluorescence and BrdU flow cytometry. Integrated cardiac untargeted metabolomics (UPLC-MS/MS) and transcriptomics (RNA-seq) were conducted to identify differential metabolites and genes following GSRd intervention. Key targets were validated by RT-qPCR and western blotting. Adeno-associated virus9 (AAV9) with cardiac-specific 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) knockdown and overexpression were employed to confirm the therapeutic targets of GSRd against MIRI. In addition, transcription factor prediction was performed by multi-platform database analysis, with subsequent chromatin immunoprecipitation-qPCR (ChIP-qPCR) providing mechanistic validation. Furthermore, molecular docking, dynamics simulation, and surface plasmon resonance (SPR) were implemented to evaluate the binding capacity between GSRd and peroxisome proliferator-activated receptor gamma (PPARG). Additionally, GW9662, a PPARG inhibitor, was used to determine the dependence of GSRd-mediated cardioprotection against MIRI on the PPARG/HMGCS2 signaling pathway. Results The results revealed that GSRd intervention substantially improved cardiac dysfunction, attenuated ventricular remodeling, ameliorated myocardial pathology, and suppressed inflammatory cytokine and oxidative stress levels in MIRI mice. Mechanistically, multi-omics analysis demonstrated enrichment in ketone body synthesis, carnitine and lipid metabolism, and PPAR signaling after GSRd treatment. Cardiac untargeted metabolomics indicated that GSRd alleviated metabolic dysregulation, concomitant with increased cardiac β-hydroxybutyrate (β-OHB). Transcriptomics identified upregulated ketogenic enzyme gene Hmgcs2 following GSRd intervention. Critically within the infarct and border zones, GSRd concurrently upregulated HMGCS2 expression and β-OHB levels while enhancing cardiomyocyte proliferation. Furthermore, cardiac-specific Hmgcs2 knockdown significantly impaired cardiomyocyte regeneration and attenuated the cardioprotective effects of GSRd in MIRI mice. Conversely, cardiac-specific Hmgcs2 overexpression promoted cardiomyocyte proliferation and recapitulated GSRd’s cardioprotective effects. Transcription factor prediction and ChIP-qPCR analyses verified direct binding of PPARG to the promoter region of Hmgcs2. Molecular docking, dynamics simulation, and SPR confirmed high-affinity binding between GSRd and PPARG. In addition, PPARG inhibition by GW9662 markedly inhibited HMGCS2 expression, suppressed cardiac regeneration, and counteracted the cardioprotective benefits of GSRd, establishing the essential role of the PPARG/HMGCS2 axis. Conclusion Collectively, this study demonstrates that GSRd ameliorates MIRI by facilitating cardiac regeneration via PPARG/HMGCS2-driven ketone body metabolic reprogramming. Thus, these findings may offer clinicians a novel therapeutic perspective in the management of MIRI.

This study aims to elucidate the dual role of lysosomal homeostasis in regulating autophagic flux during myocardial ischemia/reperfusion injury (MIRI). Using a rat MIRI model and primary myocardial cell hypoxia/reoxygenation (HR) model, we assessed the changes in autophagic flux through the intervention of autophagy agonists (TAT-Beclin1), inhibitors (3-MA), lysosomal agonists (Torin1), and inhibitors (Bafilomycin A1) from multiple dimensions. In vitro experiments showed that HR significantly induced the accumulation of autophagosomes, but lysosomal dysfunction resulted in blocked autophagic flux. Intervention with Torin1 increased the autophagolysosome formation rate, while simultaneously reducing cell necrosis (Hoechst/PI staining) and apoptosis (flow cytometry of Annexin V + cells), whereas BafA1 exacerbated the damage. In vivo studies confirmed that after IR, the infarct size increased, and left ventricular ejection fraction (LVEF) decreased. However, 3-MA and Torin1 interventions reduced infarct size and partially restored ejection fraction. Mechanistically, Western blot analysis showed that after HR, SQSTM1/p62 and LC3 accumulated, while LAMP1 degradation occurred. Lysosomal activation alleviated the HR-induced accumulation of autophagic vesicles. This study reveals a vicious cycle of “overactivation of autophagy - lysosomal degradation defects” in MIRI, and targeting lysosomal homeostasis to regulate autophagic flux may serve as a novel therapeutic strategy.

This study aimed to investigate the therapeutic effect and underlying mechanism of Guizhi Tongluo Tablets in myocardial ischemia-reperfusion injury(MIRI)by regulating the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway and inhibiting inflammatory response.Sixty healthy SPF-grade male C57BL/6J mice were randomly divided into sham group,model group,low-dose Guizhi Tongluo Tablets group,medium-dose Guizhi Tongluo Tablets group,high-dose Guizhi Tongluo Tablets group,and nicorandil group.The MIRI model was established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion.Beginning on day 1 after the operation,the mice in the low-,medium-,and high-dose Guizhi Tongluo Tablets groups received 0.51,1.03,and 2.06 g·kg-1·d-1 by gavage,respectively.Mice in the nicorandil group were administered 2.28 mg·kg-1·d-1 by gavage.Mice in the sham group and the model group received an equal volume of normal saline once daily by gavage for four consecutive weeks.Cardiac function was assessed via echocardiography.Laser speckle contrast analysis(LASCA)was used to evaluate the microvascular reperfusion in each group.Hematoxylin-eosin(HE)staining was used to observe pathological changes in cardiac tissue,while TUNEL staining was used to detect the apoptosis of cardiomyocytes.The expression levels of inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the myocardium were measured by qPCR and enzyme-linked immunosorbent assay(ELISA).Transcriptomic sequencing was conducted to identify differentially expressed genes,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was used to determine the related pathways.The protein expression levels of PI3K,phosphorylated PI3K(p-PI3K),Akt,and phosphorylated Akt(p-Akt)were analyzed using the Jess automated protein analysis system.The results showed that compared with the sham group,the model group exhibited significantly reduced left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),increased infiltration of inflammatory cells in the heart tissue,disorganized cardiomyocyte arrangement,and significantly increased cardiomyocyte apoptosis.Expression levels of IL-1β,IL-6,and TNF-α were markedly upregulated,while the ratios of p-PI3K/PI3K and p-Akt/Akt were significantly decreased.Compared with the model group,mice in the Guizhi Tongluo Tablets groups showed significantly improved cardiac function,reduced inflammatory cell infiltration,partially restored cardiac structure,significantly decreased cardiomyocyte apoptosis and levels of IL-1β,IL-6,and TNF-α,along with significantly increased p-PI3K/PI3K and p-Akt/Akt levels.These findings suggest that Guizhi Tongluo Tablets can effectively prevent and treat MIRI,possibly by activating the PI3K/Akt signaling pathway and alleviating cardiac inflammation.

BACKGROUND AND AIMS:The beneficial effect of pre-treatment with unfractionated heparin (UFH) at first medical contact (FMC) before primary percutaneous coronary intervention (PPCI) in all-comers with ST-elevation myocardial infarction (STEMI) remains uncertain. METHODS:HELP-PCI was an investigator-initiated, randomized controlled trial conducted at 36 clinical centres in China. Patients with STEMI presenting ≤12 h after symptom onset undergoing PPCI were randomly assigned (1:1) to intravenous administration with UFH (100 U/kg) at FMC or in the Cath Lab through a catheter sheath. The primary endpoint was Thrombolysis in Myocardial Infarction flow grade (TFG)-3 of infarct-related artery (IRA) at diagnostic angiography before PPCI. The secondary outcome was complete epicardial and myocardial reperfusion after PPCI and major adverse cardiac and cerebrovascular events (MACCE; defined as the composite of all-cause death, cardiac death, heart failure hospitalizations, re-infarction, stent thrombosis, unplanned revascularization, and stroke) at 12 months. Safety outcome was 30-day Bleeding Academic Research Consortium (BARC) type ≥2 bleeding. RESULTS:A total of 999 patients with STEMI undergoing PPCI were randomly assigned to receive either UFH administration at FMC (n = 505) or in the Cath Lab (n = 494). Pre-treated population at FMC showed a higher frequency of TFG-3 of IRA compared with the Cath Lab group (23.6% vs 17.6%; odds ratio, 1.44; 95% confidence interval, 1.06-1.97; P = .02). There were no significant differences in secondary endpoints or in the safety endpoint, including 12-month MACCE, complete epicardial and myocardial reperfusion, and major bleeding. CONCLUSIONS:Pre-treatment with loading-dose UFH at FMC was associated with an improvement of spontaneous reperfusion of IRA without increasing the risk of major bleeding.

Background: The effects of dietary niacin on the risk of cardiovascular disease (CVD) and mortality in patients with chronic kidney disease (CKD) remain unclear. Methods: CKD patients with estimated glomerular filtration rates (eGFRs) 20–59 mL/min/1.73 m2 or urinary albumin/creatinine ratio ≥30 mg/g were identified in the National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2018. Age, gender, race, education level, marital status, body mass index, blood pressure, and smoking and drinking history were considered as confounders. Results: The present study encompassed 3815 CKD patients eligible for inclusion based on the study criteria. Participants with a niacin intake of >27.7 mg/d (quartile 4) had a lower prevalent CVD risk than those with an intake of ≤14.67 mg (quartile 1) (odds ratio (OR), 0.710, 95% CI: 0.560–0.900; p for trend = 0.004). In the follow-up with a median of 7.0 years, 323 from CVD. After adjustment, a higher niacin intake (>27.7 mg) reduced CVD mortality compared to a lower intake (≤14.67 mg) (hazard ratio (HR), 0.610, 95% CI: 0.480–0.770; p for trend <0.001). Adding dietary niacin to clinical variables increased the C-index from 0.746 to 0.749 for CVD prevalence and from 0.659 to 0.682 for mortality. The net reclassification improvement increased by 9.0% and 13.1% for CVD and mortality, respectively, and the integrated discrimination improvement increased by 0.3% and 1%, respectively. Conclusions: Higher dietary niacin intake may reduce CVD and its mortality in individuals with CKD.

BackgroundEffective therapies for pulmonary fibrosis caused by coronavirus disease (COVID-19) and other etiologies are lacking. Our previous studies demonstrated that Fuzheng Huayu tablet (FZHY), a traditional Chinese medicine known for its anti-liver fibrotic properties, can improve lung function in patients with chronic obstructive pulmonary disease and attenuate bleomycin-induced pulmonary fibrosis in rats.PurposeThis study aimed to evaluate the efficacy and safety of FZHY in post-COVID-19 pulmonary fibrosis.MethodsA multi-center, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy of a 24-week treatment with FZHY, combined with vitamin C and respiratory function rehabilitation, for treating pulmonary fibrosis in discharged convalescent COVID-19 patients. The primary outcome was the regression rate of pulmonary fibrosis assessed by the high-resolution computed tomography scores and lung function improvement (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], and FEV1/FVC) after 24 weeks. Secondary outcomes included the 6-min walk distance, improvement in pulmonary inflammation, clinical symptoms, and quality of life.ResultsThis study included 142 patients, who were randomized to the FZHY (n = 72) and placebo groups (n = 70). By week 24, the regression rates of pulmonary fibrosis in the FZHY and placebo groups were 71.2% and 49.2%, respectively (p = 0.01). Limited spirometry data revealed higher FEV1/FVC in the FZHY group than in the placebo group at week 8 ([87.7 ± 7.2] % vs. [82.7 ± 6.9] %; p = 0.018). The regression rates in pulmonary inflammation in the FZHY and placebo groups were 83.8% and 68.8%, respectively (p = 0.04). At week 4, the increase in 6-min walking distance was greater in the FZHY group than in the placebo group ([41.4 ± 64.1] m vs. [21.8 ± 50.3] m; p = 0.05). However, no significant differences were observed between the groups in the improvement rate of clinical symptoms, quality of life-BREF, patient health questionnaire-9, or generalized anxiety disorder-7 scores (p > 0.05). No drug-related adverse events were reported in the FZHY group.ConclusionFZHY attenuates post-COVID-19 pulmonary fibrosis, with good safety profiles.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT04279197, identifier NCT04279197.

Myocardial ischemia/reperfusion (I/R)-induced cell death, such as autophagy and ferroptosis, is a major contributor to cardiac injury. Regulating cell death may be key to mitigating myocardial ischemia/reperfusion injury (MI/RI). Autophagy is a crucial physiological process involving cellular self-digestion and compensation, responsible for degrading excess or malfunctioning long-lived proteins and organelles. During MI/RI, autophagy plays both "survival" and "death" roles. A growing body of research indicates that ferroptosis is a type of autophagy-dependent cell death. This article provides a comprehensive review of the functions of autophagy and ferroptosis in MI/RI, as well as the molecules mediating their interaction. Understanding the link between autophagy and ferroptosis may offer new therapeutic directions for MI/RI, bearing significant clinical implications. Autophagy and ferroptosis-induced cell death are important causes of myocardial ischemia-reperfusion injury(MI/RI), and targeted modulation of cell death may be key to attenuating I/R injury. Increasing evidence suggests that autophagy, especially selective autophagy, plays an important role in promoting ferroptosis. There may be interactions between various selective autophagy that constitute a complex regulatory network between autophagy and ferroptosis, such as ferritinophagy, mitophagy, lipophagy, clockophagy, and chaperone-mediated autophagy (CMA). In addition, there are co-regulatory molecules of autophagy and ferroptosis during MI/RI, including Becline 1, NRF2, AMPK, mTOR, P53, PKA, AKT, STAT3, ERK1/2, and HIF. To date, the relationship between ferroptosis and autophagy in MI/RI is still in the preliminary research stage, and further studies will reveal the relationship between the two. Further studies in the future to clarify the interaction between autophagy and ferroptosis may provide a new direction for the treatment of MI/RI, which is of great clinical significance.

In recent years, the interaction of intracellular organelles such as mitochondria and lysosomal functions has attracted increasing attention. Recent evidence suggests that mitochondrion-lysosomal contact plays a key role in regulating lysosomal biogenesis and maintaining cellular homeostasis. Myocardial ischemia and reperfusion will lead to corresponding changes in the autophagy flux in cardiomyocytes, and lysosomes are a key link in the process of autophagy, and the fusion of lysosomes and autophagosomes is an essential link in the occurrence of autophagy. Therefore, the function and homeostasis of lysosomes also undergo different changes during myocardial ischemia and reperfusion. Lysosomal-related biological factors and membrane proteins also play different roles. This article will review the mechanism of lysosomes in myocardial ischemia-reperfusion injury and the research progress of lysosomal-related proteins.

This study aims to assess the associations of admission systolic blood pressure (SBP) level with spontaneous reperfusion (SR) and long-term prognosis in ST-elevation myocardial infarction (STEMI) patients. Data from 3809 STEMI patients who underwent primary percutaneous coronary intervention within 24 h, as recorded in the Chinese STEMI PPCI Registry (NCT04996901), were analyzed. The primary endpoint was SR, defined as thrombolysis in myocardial infarction grade 2–3 flow of IRA according to emergency angiography. The second endpoint was 2-year all-cause mortality. The association between admission BP and outcomes was evaluated using Logistic regression or Cox proportional hazards models with restricted cubic splines, adjusting for clinical characteristics. Admission SBP rather than diastolic BP was associated with SR after adjustment. Notably, this relationship exhibits a nonlinear pattern. Below 120mmHg, There existed a significant positive correlation between admission SBP and the incidence of SR (adjusted OR per 10-mmHg decrease for SBP ≤ 120 mm Hg: 0.800; 95