INTRODUCTION:Severe coronary artery calcification (CAC) can complicate percutaneous coronary intervention (PCI) and is associated with less favourable procedural and clinical outcomes. Rotational atherectomy (RA) and orbital atherectomy (OA) are established calcium-modification strategies used to facilitate PCI in heavily calcified lesions. This systematic review and meta-analysis evaluated the comparative clinical and procedural outcomes of RA and OA in patients with severe CAC. METHODS:This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidance. PubMed, EMBASE, and CENTRAL were searched from inception to July 2026 for studies directly comparing RA and OA in patients undergoing PCI for severe CAC. Eligible studies were synthesised quantitatively where appropriate and narratively otherwise. Risk of bias was evaluated using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2 tool for the randomised controlled trial. RESULTS:No statistically significant differences between RA and OA were identified for short-term major adverse cardiovascular events (MACE), short- or long-term all-cause mortality, cardiac mortality, long-term nonfatal myocardial infarction (MI) or short-term target vessel revascularisation (TVR). Compared with OA, RA was associated with higher odds of long-term MACE (OR 1.51, 95% CI 1.01-2.26), short-term nonfatal MI (OR 1.77, 95% CI 1.05-2.98) and long-term TVR (OR 2.51, 95% CI 1.12-5.64). Conversely, coronary dissection occurred less frequently with RA (OR 0.38, 95% CI 0.20-0.72). There were no significant between-group differences in cardiac tamponade, device-induced coronary perforation, slow-flow/no-reflow, fluoroscopy time or contrast volume. CONCLUSION:In this updated meta-analysis of more than 80,000 patients, OA was associated with lower pooled rates of long-term MACE, short-term nonfatal MI and long-term TVR, whereas RA was associated with a lower rate of coronary dissection. No consistent difference in all-cause mortality was demonstrated. Given the predominantly observational evidence base, these associations should not be interpreted as evidence of causal superiority, and device selection should remain individualised according to lesion characteristics, intravascular imaging findings and operator expertise.
Connective tissue growth factor (CTGF), also known as CCN2, is a matricellular protein of the CCN family (CCN1-6) that regulates the proliferation of vascular smooth muscle cells (VSMCs), thereby contributing to the pathogenesis of atherosclerosis and hypertension. However, the intercellular signaling pathway that CTGF takes for vascular remodeling, such as VSMC phenotype transition, has not been fully elucidated. This study employed a combination of in vivo and in vitro tests to examine VSMC phenotype and reveal the role of CTGF in vascular remodeling induced by angiotensin II (Ang II). The in vitro experiments showed that Ang II upregulated CTGF expression in rat VSMCs in a concentration- and time-dependent manner. Genetic depletion of CTGF with siRNA against rat Ccn2 prevented Ang II-induced autophagic flux impairment. In addition, Ang II-induced phenotypic switch was inhibited by 3-MA, an inhibitor of autophagy, suggesting CTGF is involved in Ang II-induced phenotypic switch via regulating autophagic flux impairment. In addition, this CTGF-dependent autophagy regulation was involved in Ang II-induced mitochondrial dysfunction in VSMCs. Moreover, anti-CTGF antibody treatment inhibited neointimal hyperplasia in a mouse model of carotid artery ligation-induced neointima formation suggesting a novel perspective role of CTGF in the phenotype switching of VSMCs and the neointimal proliferation process. These results offer insights into the effect of anti-CTGF on preventing autophagic flux impairment and VSMC phenotype switching caused by mitochondrial dysfunction in vascular diseases associated with aberrant VSMC proliferation.
OBJECTIVE:Based on the FDA Adverse Event Reporting System (FAERS) database, data mining of adverse event (AE) signals related to anthracyclines was conducted to explore their potential medication risks, especially cardiotoxicity, in order to promote the rational and safe use of these drugs in clinical practice. METHODS:AE data for anthracyclines (represented by aclarubicin, daunorubicin, doxorubicin, and epirubicin) commonly used to treat hematologic malignancies and solid tumors were retrieved from the FAERS database from January 1, 2004, to June 30, 2025. Disproportionation analysis was primarily used to mine signals of AEs related to anthracyclines. RESULTS:A total of 324 AE reports related to aclarubicin, 298 related to daunorubicin, 822 related to doxorubicin, and 334 related to epirubicin were extracted from the FAERS database. Based on risk signal detection using the Bayesian confidence propagation neural network (BCPNN) for cardiac AEs: For aclarubicin, left ventricular dysfunction exhibited the strongest risk signal among AEs with positive risk signals, whereas cardiac failure had the largest number of reports. For daunorubicin, supraventricular arrhythmia represented the strongest risk signal among AEs with positive risk signals, and tachycardia had the highest reporting count. For doxorubicin, acute cardiomyopathy showed the strongest risk signal among AEs with positive risk signals, whereas cardiac failure possessed the greatest number of reports. For epirubicin, heart failure with midrange ejection fraction yielded the strongest risk signal among AEs with positive risk signals, and cardiac failure had the largest number of reports. CONCLUSION:This study provides a more comprehensive insight into the monitoring, supervision, and management of adverse reactions related to anthracyclines. Clinicians should further focus on the impact of various AEs related to anthracyclines and their corresponding signal strengths, especially the cardiotoxicity of anthracyclines, which is of great value for improving the clinical safety of anthracyclines.
INTRODUCTION AND OBJECTIVES:Calcified coronary lesions are associated with an increased risk of percutaneous coronary intervention (PCI) failure. Despite the availability of several calcium-modification strategies and randomized trials evaluating their efficacy, comparative investigations remain scanty. The aim of the present analysis is to assess the comparative performance of calcium-modification strategies in patients undergoing PCI of calcified coronary lesions. METHODS:We conducted a systematic search for randomized trials evaluating calcium-modification strategies in patients undergoing PCI. Random-effects network meta-analyses were performed. The primary outcome was minimal stent area (MSA). Secondary outcomes included all-cause death and stent thrombosis. RESULTS:Twenty-two trials enrolling 4855 patients were included. Compared to calcium modification with noncompliant balloons, the use of cutting/scoring balloon (mean difference: 0.81 mm2, 95% confidence interval: [0.36, 1.27]; p = 0.001), super high-pressure balloon (SHPB, 0.95 mm2 [0.18, 1.72]; p = 0.016), intravascular lithotripsy (IVL, 0.87 mm2 [0.40, 1.34]; p < 0.001), rotational atherectomy (RA, 0.90 mm2 [0.30, 1.50]; p = 0.003), and RA plus cutting balloon (1.24 mm2 [0.46, 2.02]; p = 0.002) led to larger MSA. According to a network ranking analysis, RA, SHPB, and IVL were possibly the best treatment options in terms of MSA. There were no significant differences in clinical outcomes between calcium-modification strategies. CONCLUSIONS:Compared with standard noncompliant balloons, RA and balloon-based strategies improved the mechanical performance of PCI in calcified coronary lesions. However, this did not result in better clinical outcomes.
BACKGROUND:Coronary atherosclerosis (CA) is a leading cause of cardiovascular morbidity and mortality worldwide. This study is aimed at identifying candidate plasma proteins and potential therapeutic targets for CA. METHODS:We performed a proteome-wide Mendelian randomization (MR) analysis using integrated protein quantitative trait loci (pQTLs) and genome-wide association study (GWAS) summary data. Forward two-sample MR was first performed using cis-pQTLs from the UK Biobank Pharma Proteomics Project (UKB-PPP), followed by reverse MR analysis to exclude potential reverse causality. Bayesian colocalization analysis was conducted to ensure that the associations between proteins and CA were driven by shared genetic variants. Summary-data-based MR (SMR) combined with HEIDI testing was used to prioritize proteins and eliminate linkage bias. Significant proteins were cross-referenced with a curated druggable genome to identify their potential therapeutic relevance. Cross-platform validation was performed using the SomaScan-based pQTL dataset from deCODE genetics. An oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) injury model was used for the evaluation of prioritized proteins. RESULTS:Forward MR analysis using UKB-PPP cis-pQTL data identified 45 CA-associated proteins (23 protective, 22 risk-related; FDR < 0.05), with no reverse causality observed. Five proteins-PARP1, SDCCAG8, FST, FOLH1, and NCAN-were prioritized through MR (FDR < 0.05), colocalization analysis (PP.H4 > 0.50), and SMR analysis with HEIDI filtering (p_SMR < 0.05; p_HEIDI > 0.05). All five proteins were included in the druggable genome list, supporting their potential therapeutic relevance. PARP1 showed consistent associations across Olink and SomaScan platforms and was upregulated in an ox-LDL-induced HUVEC model as assessed by western blot. CONCLUSIONS:This study identified PARP1, SDCCAG8, FST, FOLH1, and NCAN as genetically prioritized candidate proteins for CA, with PARP1 showing the most consistent evidence across analyses. Further validation and mechanistic studies are warranted.
BACKGROUND:Apolipoprotein B (ApoB) is widely recognized as a biomarker significantly associated with cardiovascular risk. However, the correlation between ApoB and the severity of coronary artery anatomical stenosis (Gensini score) in individuals aged 45 and above has not been fully studied. METHODS:A cross-sectional retrospective analysis was conducted, involving 818 patients who underwent coronary angiography. Fasting blood samples were collected to measure lipid parameters, including ApoB. The severity of coronary artery stenosis was assessed using the Gensini score, and patients were divided into two groups based on the median cut-off (<36 vs. ≥ 36). A multivariate regression model was used to evaluate the association between ApoB and the severity of stenosis after adjusting for potential confounding factors. RESULTS:Compared to the mild stenosis group (Gensini score < 36), the moderate-to-severe stenosis group (score ≥ 36) had significantly higher levels of ApoB (1.0 ± 0.3 vs. 0.9 ± 0.3 g/L) and LDL-c (p < 0.05), while HDL-c and ApoA levels were lower (p < 0.001). Multivariate regression analysis indicated that ApoB was independently associated with moderate-to-severe coronary stenosis (β = 46.1, 95% CI: 31.3-61.0 p < 0.001). Sensitivity analysis using continuous Gensini score confirmed the association (β = 22.57, 95% CI: 13.67-31.47, p < 0.0001). Dose-response analysis revealed that higher ApoB tertiles were associated with progressively higher Gensini scores (P for trend = 0.001). Stratified analysis revealed a consistent positive correlation between ApoB and Gensini scores across all clinical subgroups (all p < 0.05), with no significant interactions detected (all P for interaction > 0.05). CONCLUSION:ApoB levels are significantly positively correlated with the severity of coronary artery stenosis in the population aged ≥ 45 years, indicating its potential clinical application value in evaluation.
BACKGROUND:Atrial fibrillation (AF) is the predominant arrhythmia. Growing evidence indicates that immunological diseases may play a role in its development. This study combined observational and genetic analyses to investigate how T-lymphocyte subsets and immunomodulatory drug targets influenced AF risk. METHODS AND RESULTS:This study retrospectively analyzed T lymphocyte subsets in 302 AF patients and 183 healthy controls. After balancing covariates via 1:1 propensity score matching, multivariate regression revealed AF patients had significantly higher absolute counts of Th1 and Th17 cells, and higher Th1/Th2 and Th17/Treg ratios (p < 0.05). A subsequent two-sample Mendelian randomization (MR) analysis, which assessed 731 immune traits and included drug-target MR, established causal relationships. It showed that increased counts of CD4+CD8dim T cells (OR = 1.03, p = 0.002) and IgD-CD38dim B cells (OR = 1.06, p = 0.0003) elevated AF risk. Furthermore, IL-6R-mediated CRP elevation increased AF risk (OR = 1.33, p = 5.18E-7), whereas higher IL-18 gene expression was protective (OR = 0.95, p = 0.036). CONCLUSION:Immune dysfunction, especially T lymphocyte subsets, is a risk factor for the development of AF. The IL-6R signaling pathway may be a potential target for AF prevention, whereas the use of IL-18 inhibitors may increase the risk of AF.
AIM:The aim of this study is to examine the effect of magnesium depletion score (MDS) on the relationship between tobacco exposure and depression in older patients with heart failure (HF). METHODS:Data from the National Health and Nutrition Examination Surveys (NHANES, 2005-2018) were analyzed in this cross-sectional study. Weighted logistic regression models were used to assess associations between MDS, tobacco exposure, and depression. Propensity score matching (PSM) was applied to minimize potential confounding. RESULTS:Among 554 eligible participants, 166 presented with depression. After covariate adjustment, quitting smoking (robustness OR = 2.179, 95% CI: 1.190-3.685), current smoking (robustness OR = 1.941, 95% CI: 0.904-3.770), and serum cotinine ≥3 ng/mL (robustness OR = 1.968, 95% CI: 0.986-3.590) were significantly associated with increased depression risk. After PSM, quitting smoking (OR = 2.16, 95% CI: 1.13-4.12) and cotinine ≥3 ng/mL (OR = 2.47, 95% CI: 1.06-5.75) remained significantly associated with depression. Compared with MDS ≤ 2 combined with no smoking, MDS ≤ 2 combined with quitting smoking (robustness OR = 2.375, 95% CI: 1.076-4.739) and MDS > 2 combined with quitting smoking (robustness OR = 3.142, 95% CI: 1.413-5.824) or currently smoking (robustness OR = 5.608, 95% CI: 1.790-13.661) were all linked to higher odds of depression. A significant multiplicative interaction between MDS and smoking was observed with p < 0.001. Also, MDS > 2 combined with serum cotinine ≥3 ng/mL was associated with higher odds of depression compared with MDS ≤ 2 combined with serum cotinine < 0.05 ng/mL (robustness OR = 5.258, 95% CI: 1.869-11.546). CONCLUSION:MDS appears a possible interaction on the association between self-reported tobacco exposure and depression. Whether maintaining adequate magnesium status can help reduce depression risk in HF patients needs further validation.
BACKGROUND AND AIMS:Patients with three-vessel coronary artery disease (3V-CAD) remain at heterogeneous risk for major adverse cardiovascular and cerebrovascular events (MACCE) after revascularization. Magnetocardiography (MCG) is a noncontact and radiation-free technique that may capture electrophysiological abnormalities not reflected by anatomical risk scores. This study evaluated the exploratory prognostic value of MCG-derived parameters in patients with 3V-CAD. METHODS:This single-center prospective cohort study included 544 patients with 3V-CAD who underwent coronary revascularization. MCG recordings were obtained before revascularization using a 36-channel optically pumped magnetometer-based system. The primary endpoint was MACCE, defined as cardiac death, stroke, myocardial infarction, or unplanned revascularization. Cox regression models were constructed using clinical variables, SYNTAX score, and an MCG composite variable. Model performance was assessed using discrimination, calibration, decision curve analysis, and bootstrap internal validation. RESULTS:During a median follow-up of 725 days, 37 patients (6.8%) experienced MACCE. The SYNTAX score was independently associated with MACCE after adjustment for clinical variables and MCG score (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.04-1.12; p < 0.001). The MCG composite variable was also associated with MACCE after adjustment for clinical variables and SYNTAX score (HR, 2.74; 95% CI, 1.57-4.79; p < 0.001). Model discrimination increased from 0.596 for clinical variables alone to 0.682 after adding SYNTAX score and to 0.727 after adding MCG. However, the improvement from the clinical + SYNTAX model to the MCG-added model was not statistically significant (p = 0.17). Bootstrap validation showed an optimism-corrected C-index of 0.672. CONCLUSION:MCG-derived parameters were associated with MACCE and may provide complementary electrophysiological information for exploratory risk stratification in patients with 3V-CAD after revascularization. Larger multicenter studies with external validation are needed to confirm its complementary prognostic value. TRIAL REGISTRATION:Chinese Clinical Trial Registry identifier: ChiCTR2200066942.
BACKGROUND:Nonvalvular atrial fibrillation (NVAF) is a prevalent arrhythmia associated with an increased risk of ischemic stroke. This study is aimed at assessing the clinical significance of echocardiographic left atrial (LA) stiffness and developing a nomogram integrating clinical and echocardiographic parameters to evaluate individualized stroke risk in NVAF patients. METHODS:We enrolled 402 consecutive NVAF patients between January 2020 and March 2023. Clinical and echocardiographic data were collected, and patients were randomly assigned to training (n = 281) and validation (n = 121) datasets. Univariate and multivariate logistic regression identified independent stroke risk factors, which were used to construct a nomogram. Model performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. The reclassification ability of the nomogram was assessed using integrated discrimination improvement (IDI) and net reclassification improvement (NRI). RESULTS:Logistic regression identified LA stiffness, LA reservoir strain, hypertension, peripheral vascular disease, and anticoagulation as independent factors associated with stroke. The nomogram based on these factors showed excellent discrimination, with a C-statistic of 0.889 (0.847-0.924) in the training cohort and 0.880 (0.808-0.932) in the validation cohort. Model A (LA stiffness, LA reservoir strain, hypertension, peripheral vascular disease, and anticoagulation) provided better net reclassification and integrated discrimination than Model B (LA stiffness, LA reservoir strain, hypertension, and peripheral vascular disease) despite both outperforming the CHA2DS2-VASc model. LA stiffness was inversely correlated with left atrial appendage (LAA) emptying (R = -0.52, p < 0.01) and filling velocities (R = -0.50, p < 0.01). Patients with LA thrombus or spontaneous echocardiographic contrast exhibited significantly higher LA stiffness (p < 0.05). CONCLUSION:A nomogram incorporating LA stiffness, LASr, hypertension, and peripheral vascular disease can effectively identify the risk of stroke in NVAF patients. Additionally, a secondary model including anticoagulation showed further improved performance but requires prospective validation. Elevated LA stiffness might play a role in the development of stroke in NVAF by influencing LA appendage hemodynamics.
Core to advancing the study of traditional Chinese medicine (TCM) mechanisms is the integrated "computational prediction-experimental verification" strategy, which enables the precise identification of therapeutic targets through multilevel technological integration. Within this framework, this study systematically investigates the therapeutic mechanisms of Shengmai injection (SMI) against heart failure following myocardial infarction (MI). Initially, using network pharmacology approaches, we systematically screened TCMSP, BATMAN, and disease databases to identify 237 common targets of SMI and chronic heart failure. Through Cytoscape-based network topology analysis, we pinpointed 52 core targets, with KEGG pathway enrichment analysis revealing the PI3K-AKT signaling pathway as the crucial pathway. Subsequently, molecular docking technology demonstrated strong binding affinity (calculated affinity: -6.171 kcal/mol) between vitamin E (an active constituent by network pharmacology analysis) and the core target AKT1. At the experimental validation level, we established a mouse MI model by ligating the left anterior descending coronary artery, with continuous administration of SMI for 4 weeks. Experimental results showed that SMI significantly improved cardiac function of chronic heart failure, reduced myocardial fibrosis, inhibited cardiomyocyte apoptosis, and promoted macrophage polarization toward the reparative M2 phenotype. In the H9c2 cell model, SMI effectively improves mitochondrial function of cardiac cells induced by H2O2 and inhibits reactive oxygen species accumulation and mitochondrial membrane potential collapse. Mechanistic studies revealed that SMI regulates mitochondrial dysfunction by activating the AKT/Bcl-2 signaling axis, upregulating Bcl-2 expression, and inhibiting Bax. Through systematic methodological integration, this study not only elucidates the mechanism by which SMI inhibits mitochondrial dysfunction and macrophage polarization and attenuates ventricular remodeling through the AKT/Bcl-2 pathway but also provides a referential multidisciplinary research paradigm for investigating the mechanisms of TCM formulations.
Managing acute coronary syndrome (ACS) and atherosclerotic cardiovascular disease remains clinically challenging, requiring a careful balance between ischemic protection and bleeding risk. Antiplatelet therapy is central to the management, with aspirin serving as the cornerstone; however, selection of the second antiplatelet agent in dual antiplatelet therapy (DAPT) remains complex. Clopidogrel, a purinergic receptor subtype Y, G protein-coupled, 12 (P2Y12) inhibitor, is widely used but is limited by substantial interindividual variability in antiplatelet response, particularly in populations with a high prevalence of CYP2C19 loss-of-function polymorphisms. These limitations prompted the development of more potent P2Y12 inhibitors, including prasugrel and ticagrelor, which provide faster and more consistent platelet inhibition. However, clinical experience-especially in Asian populations-has highlighted that a "one-size-fits-all" dosing strategy may not be appropriate, as heightened bleeding risk can offset ischemic benefit. This review reexamines the contemporary role of prasugrel, focusing on evidence supporting dose optimization, careful patient selection, and population-specific considerations. Current evidence suggests that prasugrel remains a valuable antiplatelet option when tailored to individual ischemic and bleeding risks, particularly in patients undergoing complex percutaneous coronary intervention and selected Asian populations requiring individualized antiplatelet strategies.
BACKGROUND:Beta-blockers are regarded as one of the primary treatment options for acute coronary syndrome (ACS) patients with reduced left ventricular ejection fraction (LVEF). However, there is ongoing debate about their therapeutic efficacy in patients with non-reduced LVEF (≥ 40%). OBJECTIVE:To determine the impact of long-term beta-blocker administration on major adverse cardiovascular events (MACE) in ACS patients with LVEF ≥ 40%. METHODS:A thorough literature search across four databases was conducted to identify eligible studies comparing beta-blocker therapy with placebo or no medication in addition to standard ACS pharmacotherapy. The outcomes of interest included all-cause mortality and MACE (comprising cardiovascular mortality, recurrent myocardial infarction [Re-MI], stroke, rehospitalization for heart failure, and revascularization). Based on LVEF values, patients were divided into three groups: (1) LVEF > 40%, (2) 40% < LVEF < 50%, and (3) LVEF ≥ 50%, and the random-effects meta-analysis estimated the risk ratios (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs). RESULTS:Five randomized controlled trials (RCTs) and 19 observational studies met the inclusion criteria. Within the RCTs, beta-blocker use was associated with a non-significant 6% reduction in MACE (RR = 0.94, 95%CI = 0.87-1.02, I2 = 19.1%). The pooled analyses of observational studies showed no significant overall impact of beta-blocker use on endpoint outcomes. Subgroup analyses revealed a reduction in MACE (HR = 0.75, 95%CI = 0.59-0.95, I2 = 0%) and Re-MI (HR = 0.45, 95%CI = 0.23-0.89) in patients with LVEF 40%-49%; however, these findings were derived primarily from observational data. Patients with LVEF ≥ 50% did not appear to benefit from long-term beta-blocker use. CONCLUSION:Long-term beta-blocker use did not show a significant benefit in patients with preserved ejection fraction (LVEF ≥ 50%). Observational data suggested a possible reduction in MACE and Re-MI in the LVEF 40%-49% subgroup; however, this finding requires confirmation in dedicated RCTs. Future larger RCTs are needed to clarify the role of beta-blockers in this borderline population.
BACKGROUND:Neoatherosclerosis (NA) and treatment modality may influence outcomes in patients with in-stent restenosis (ISR). This study evaluated the prognostic impact of different NA patterns and percutaneous coronary intervention (PCI) strategies guided by optical coherence tomography (OCT). METHODS:We retrospectively analyzed 288 ISR lesions with OCT-defined NA treated between January 2015 and December 2023. Lesions were classified as lipidic, calcified, or mixed NA. The primary endpoint was 1-year target lesion failure (TLF), defined as a composite of cardiac death, nonfatal myocardial infarction, and clinically driven target lesion revascularization (CD-TLR). Cox regression, interaction analysis, and propensity score matching (PSM) were performed. RESULTS:No significant differences in TLF (p = 0.420) or CD-TLR (p = 0.650) were observed among NA patterns. After adjustment for clinical and procedural covariates, DES reimplantation was associated with a lower risk of TLF (hazard ratio [HR] 0.390, 95% confidence interval [CI] 0.157-0.974; p = 0.044) and CD-TLR (HR: 0.341, 95% CI: 0.114-0.925; p = 0.039) compared with DCB angioplasty. In patients with lipidic NA, a similar trend was observed (TLF: HR: 0.287; 95% CI: 0.097-0.849; p = 0.024; CD-TLR: HR: 0.171; 95% CI: 0.039-0.750; p = 0.019). However, no significant interaction was observed between the NA pattern and treatment modality (p for interaction = 0.543). CONCLUSION:No significant differences in clinical outcomes were observed across NA patterns. Although DES showed numerically favorable outcomes in lipidic NA, no significant interaction between NA pattern and treatment modality was detected. And these findings are hypothesis-generating and may relate to the additional mechanical scaffolding and plaque sealing provided by DES in lipidic NA.
Lycorine (LYC), the most abundant monomeric compound from Lycoris radiata bulbs, possesses a range of biological activities, including antipulmonary fibrosis and cardioprotective effects. However, its role in regulating pathological cardiac remodeling, particularly in cardiac fibrosis, remains unclear. In this study, we used transforming growth factor-β1 (TGF-β1) to stimulate NIH/3T3 cells and primary rat cardiac fibroblasts, which were in vitro models of pathological fibroblast activation, and established a mouse model of cardiac fibrosis via intraperitoneal injection of doxorubicin (DOX). The effects of LYC on TGF-β1-induced fibroblast activation and migration were assessed using Western blotting, quantitative PCR, scratch assays, and EdU staining. Cardiac damage and fibrosis were evaluated in vivo by echocardiography, enzyme-linked immunosorbent assay (ELISA), and Masson’s trichrome staining. Through transcriptomic sequencing and bioinformatic analyses, proline-rich tyrosine kinase 2 (PYK2) was identified as a potential target of LYC. This finding was further validated using siPYK2 and the PYK2 inhibitor PF4618433 in TGF-β1-induced NIH/3T3 cells. Our results demonstrated that LYC effectively suppressed fibroblast activation, proliferation, and migration. In addition, LYC significantly ameliorated cardiac dysfunction and reduced collagen deposition in myocardial tissues, thereby attenuating the progression of cardiac fibrosis. Mechanistically, these effects were attributed to the regulation of PYK2 expression and activity by LYC. This study provides a scientific basis for understanding the mechanism of LYC in improving cardiac fibrosis and highlights PYK2 as a potential therapeutic target for the treatment of cardiac fibrosis.
BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors demonstrate significant lipid-lowering effects, but the widespread use of anti-PCSK9 monoclonal antibodies remains limited.PurposeThis study is aimed at understanding patients ' real-world experiences with anti-PCSK9 monoclonal antibodies from a subjective perspective and identifying key factors influencing medication adherence.MethodsA qualitative research methodology was employed, involving face-to-face semistructured in-depth interviews with 24 individuals who had previously used anti-PCSK9 monoclonal antibodies. The interviews were guided by a thematic framework approach and recorded in their entirety. Posttranscription, Colaizzi ' s phenomenological analysis method was utilized to systematically collect and interpret patient-reported subjective experiences.ResultsAmong those continuing treatment, the most common motivating factors were the anti-PCSK9 monoclonal antibodies ' favorable efficacy and fewer adverse reactions. Among those discontinuing treatment, the primary reasons for stopping were high medication costs (62.5%), insufficient recognition of the necessity for continued use (62.5%), and unwillingness to use injection administration (68.75%). The underlying determinants of patients ' behavioral patterns can be elucidated and mitigated by applying the health belief model and the theory of planned behavior.ConclusionResearch findings indicate that patients ' willingness to use medication is primarily influenced by three factors: perceived good efficacy, health awareness, and fear of needles and economic burden. We are aimed at enhancing long-term clinical benefits for patients and improving treatment adherence, establishing education about drug efficacy and necessity, promoting innovation of nasal spray or long-acting implant formulations, and achieving precise medical insurance coverage for high-risk populations.Trial RegistrationChiCTR registration number: ChiCTR2500101339
Antithrombotic therapy in patients with nonvalvular atrial fibrillation (NVAF) undergoing percutaneous coronary intervention (PCI) is clinically challenging, with real-world strategies often remaining inconsistent. This study analyzed 2020 annual data from the Shanghai Cardiac Intervention Quality Control Center, encompassing 23,115 patients who underwent PCI across 36 centers in Shanghai. Among these, 1306 (5.65%) patients with a confirmed diagnosis of NVAF were enrolled. Dual antiplatelet therapy (DAPT) was the most common antithrombotic regimen (584, 44.7%). Anticoagulation therapy was administered to only 478 (55.8%) of male patients with a CHA2DS2-VASc score of ≥ 2 and 207 (55.6%) of female patients with a CHA2DS2-VASc score of ≥ 3. Significant differences were observed across antithrombotic strategy groups regarding gender distribution, age, atrial fibrillation (AF) type, coronary artery disease type, and history of congestive heart failure (CHF), hypertension, stroke, or myocardial infarction (MI). Patients receiving oral anticoagulants (OACs) showed higher rates of persistent AF (53.2% vs. 33.9%, p < 0.001) and more frequent histories of CHF and stroke. Conversely, patients not receiving OAC therapy demonstrated a higher proportion of paroxysmal AF (66.1% vs. 46.8%, p < 0.001) and prior MI. A substantial gap persists between guideline recommendations and real-world antithrombotic management in Chinese AF patients undergoing PCI. Key challenges include the underutilization of OAC therapy, a high prevalence of reduced-dose anticoagulation, and a potential overreliance on DAPT. These findings highlight the urgent need to improve adherence to evidence-based guidelines and conduct personalized risk-benefit assessments.
Atherosclerotic cardiovascular disease (ASCVD), particularly myocardial infarction (MI), is the leading cause of mortality and morbidity worldwide. The pathophysiology of MI involves atherosclerotic plaque rupture with thrombus formation, interrupting myocardial blood supply with subsequent myocardial necrosis. Despite advances in primary prevention and acute revascularization strategies for MI, recurrent ischemic events and stent thrombosis continue to pose challenging issues for clinicians. Consequently, effective secondary prevention, specifically antiplatelet therapy (aspirin and P2Y12 inhibitors), is the cornerstone of the prevention of recurrent ischemia and cardiovascular death to improve long-term prognosis. However, the optimal choice and duration of antiplatelet therapy should be individualized depending on risk factors and comorbidities. This review will explore the mechanisms of thrombosis in MI, the role of antiplatelet therapy in secondary prevention after MI, and the clinical evidence supporting various antiplatelet agents, focusing on their pharmacological profiles, efficacy, safety considerations, guideline recommendations, and application in special populations based on available clinical trial data while highlighting key controversies, knowledge gaps, and emerging strategies such as biomarker-guided and genotype-guided therapy.
Patients with hypertension, especially when complicated by cardiovascular disease (CVD) and/or comorbidities, require long-term treatment with a combination of antihypertensive drugs, which often gives rise to complex drug regimens. Dual-agent combination antihypertensive therapy is recommended in most patients with hypertension, and where available, a fixed-dose single-pill combination (SPC) is recommended. The combination of antihypertensive drugs should take into account the patient's overall CVD risk profile (other CVD risk factors and diagnoses). The combination of a beta-blocker and angiotensin-converting enzyme inhibitor (ACEi) acts on two neuroendocrine systems implicated in the pathophysiology of hypertension and multiple CVD: beta-blockers on the sympathetic nervous system and ACEis on the renin-angiotensin system (RAS). A large body of solid evidence states that, in addition to their antihypertensive effects, both beta-blockers and ACEis provide cardioprotection and guarantee reductions in CV morbidity and mortality in patients with coronary artery disease (CAD), atrial fibrillation, and heart failure. For these reasons, such a combination might be beneficial for many patients. This review summarizes the evidence supporting the use of beta-blockers and ACEis, as well as the rationale behind their combined administration, particularly in patients with a high risk of CVD, such as those with ischemic heart disease, atrial fibrillation, or heart failure.
