It is essential to manage cardiovascular disease related to atherosclerosis through understanding its disease progression mechanism. The effects of the xanthine derivative KMUP-1 on alleviating atherosclerosis and cardiac remodeling, as well as its underlying mechanisms, were examined. In this study, atherosclerosis and cardiac damage were induced in ApoE knockout (KO) mice by feeding them a high-fat diet (HFD) for 12 weeks. The co- and posttreatment of KMUP-1 was evaluated. Our results showed that KMUP-1 treatment significantly reduced body weight gain in HFD-induced mice. The Oil Red O and hematoxylin–eosin staining showed that KMUP-1 reduced the aortic plaque area, intima–media thickness, and intima–lumen thickness. KMUP-1 reduced inflammatory cytokines IL-1β, TNF-α, IL-6, and MCP-1 in the serum of mice through an ELISA assay. Moreover, echocardiography evaluation indicated that KMUP-1 attenuated left ventricular cardiac hypertrophy and restored cardiac function. Further, KMUP-1 treatment suppressed proapoptotic protein Bax and reversed Bcl-2 level by promoting autophagy-related Gene 7 and autophagosome marker LC3-II activation in the vascular through immunofluorescence and western blotting assay. KMUP-1 improved the serum lipidomic profile. Both co- and posttreatment of KMUP-1 stimulated autophagy and reduced inflammation and apoptosis, against atherosclerosis and cardiac remodeling in an ApoE-KO mouse model. It suggests its potential as a therapeutic agent for cardiovascular diseases.
{"title":"Antiatherogenic and Cardioprotective Effects of a Xanthine Derivative KMUP-1 in ApoE Knockout Mice","authors":"Erna Sulistyowati, Shang-En Huang, Chih-Chieh Hsu, Yi-Chia Wu, Yu-Ying Chao, Jong-Hau Hsu, Bin-Nan Wu, Zen-Kong Dai, Ming-Chung Lin, Jwu-Lai Yeh","doi":"10.1155/cdr/8419343","DOIUrl":"https://doi.org/10.1155/cdr/8419343","url":null,"abstract":"<p>It is essential to manage cardiovascular disease related to atherosclerosis through understanding its disease progression mechanism. The effects of the xanthine derivative KMUP-1 on alleviating atherosclerosis and cardiac remodeling, as well as its underlying mechanisms, were examined. In this study, atherosclerosis and cardiac damage were induced in ApoE knockout (KO) mice by feeding them a high-fat diet (HFD) for 12 weeks. The co- and posttreatment of KMUP-1 was evaluated. Our results showed that KMUP-1 treatment significantly reduced body weight gain in HFD-induced mice. The Oil Red O and hematoxylin–eosin staining showed that KMUP-1 reduced the aortic plaque area, intima–media thickness, and intima–lumen thickness. KMUP-1 reduced inflammatory cytokines IL-1<i>β</i>, TNF-<i>α</i>, IL-6, and MCP-1 in the serum of mice through an ELISA assay. Moreover, echocardiography evaluation indicated that KMUP-1 attenuated left ventricular cardiac hypertrophy and restored cardiac function. Further, KMUP-1 treatment suppressed proapoptotic protein Bax and reversed Bcl-2 level by promoting autophagy-related Gene 7 and autophagosome marker LC3-II activation in the vascular through immunofluorescence and western blotting assay. KMUP-1 improved the serum lipidomic profile. Both co- and posttreatment of KMUP-1 stimulated autophagy and reduced inflammation and apoptosis, against atherosclerosis and cardiac remodeling in an ApoE-KO mouse model. It suggests its potential as a therapeutic agent for cardiovascular diseases.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/8419343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145406941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carvedilol, commonly used to treat hypertension and known for its vasodilatory and pleiotropic effects, has been studied in various patient populations. However, its specific impact on diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) remains unclear.
Aim
The aim of the study is to evaluate carvedilol′s efficacy in preventing concentric cardiac remodelling in at-risk individuals and modulating it in patients with HFpEF.
Methods
In adherence to PRISMA guidelines, we searched PubMed and ScienceDirect up to March 2024 using terms related to carvedilol and HFpEF. We included randomised controlled trials and prospective cohort studies published in English. Outcomes include changes in natriuretic peptides and echocardiography parameters of diastolic function. Exclusion criteria encompassed non-English studies, nonhuman studies and studies not using carvedilol or exclusively involving HFrEF patients. Risk of bias was assessed using the revised Cochrane tool and Newcastle–Ottawa Scale. Data synthesis was performed using a random-effects meta-analysis with sensitivity analyses and a leave-one-out procedure to explore heterogeneity.
Results
Eighteen studies involving 2233 participants were included. Various populations were included: those with HFpEF or undergoing cardiotoxic chemotherapy. Meta-analysis did not reveal significant effects of carvedilol on echocardiography parameters such as E/A ratio (mean difference 0.04, 95% CI −0.01 to 0.08), E/e ′ ratio (mean difference −0.50, 95% CI −1.39 to 0.39) and LVMI (mean difference 0.21, 95% CI −3.13 to 3.55), with substantial heterogeneity observed in LVEF, LVMI and BNP.
Conclusion
Carvedilol does not significantly impact diastolic dysfunction across various populations. However, the diversity of study populations and outcomes contributes to the heterogeneity of results.
{"title":"Is Carvedilol Effective in Preventing and Modulating Concentric Cardiac Remodelling? A Comprehensive Systematic Review and Meta-Analyses","authors":"Alice Valeria Wiyono, Azizah Puspitasari Ardinal","doi":"10.1155/cdr/9108324","DOIUrl":"https://doi.org/10.1155/cdr/9108324","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Carvedilol, commonly used to treat hypertension and known for its vasodilatory and pleiotropic effects, has been studied in various patient populations. However, its specific impact on diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of the study is to evaluate carvedilol′s efficacy in preventing concentric cardiac remodelling in at-risk individuals and modulating it in patients with HFpEF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In adherence to PRISMA guidelines, we searched PubMed and ScienceDirect up to March 2024 using terms related to carvedilol and HFpEF. We included randomised controlled trials and prospective cohort studies published in English. Outcomes include changes in natriuretic peptides and echocardiography parameters of diastolic function. Exclusion criteria encompassed non-English studies, nonhuman studies and studies not using carvedilol or exclusively involving HFrEF patients. Risk of bias was assessed using the revised Cochrane tool and Newcastle–Ottawa Scale. Data synthesis was performed using a random-effects meta-analysis with sensitivity analyses and a leave-one-out procedure to explore heterogeneity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighteen studies involving 2233 participants were included. Various populations were included: those with HFpEF or undergoing cardiotoxic chemotherapy. Meta-analysis did not reveal significant effects of carvedilol on echocardiography parameters such as E/A ratio (mean difference 0.04, 95% CI −0.01 to 0.08), E/e <sup>′</sup> ratio (mean difference −0.50, 95% CI −1.39 to 0.39) and LVMI (mean difference 0.21, 95% CI −3.13 to 3.55), with substantial heterogeneity observed in LVEF, LVMI and BNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Carvedilol does not significantly impact diastolic dysfunction across various populations. However, the diversity of study populations and outcomes contributes to the heterogeneity of results.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/9108324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145406706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ran Yin, Cheng-Long Wu, Si-Yang Yu, Kun Huang, Yuan Wen, Jun-Gang Nie, Ru Ying
Background
Atrial fibrosis is a key structural substrate in atrial fibrillation (AF). This work was conducted to investigate the profibrotic effects of chemokine C-X-C motif Ligand 1 (CXCL1) and elucidate the actions of endoplasmic reticulum stress (ERS) and ER-resident protein thioredoxin domain-containing Protein 5 (TXNDC5) in this process.
Methods
Serum CXCL1 concentrations were measured in patients with AF and healthy controls. The effects of CXCL1 on atrial fibrosis were evaluated using ex vivo rat atrial tissue culture. Additionally, the influence of CXCL1 on collagen synthesis, ERS activation, and TXNDC5 expression was assessed in primary rat cardiac fibroblasts. Pharmacological inhibition of ERS and gene silencing of TXNDC5 were employed to decipher underlying mechanisms.
Results
CXCL1 levels were elevated in patients with AF compared to controls. In ex vivo rat atrial tissue, CXCL1 treatment induced marked fibrosis and upregulated the expression of ERS markers GRP78 and ATF6, as well as TXNDC5. In cardiac fibroblasts, CXCL1 promoted the secretion of Collagen I, Collagen III, and TGF-β1. Notably, both ERS inhibition and TXNDC5 knockdown effectively attenuated CXCL1-induced fibroblast activation and extracellular matrix protein expression.
Conclusion
CXCL1 promotes atrial fibrosis through the activation of ERS and upregulation of TXNDC5, potentially contributing to atrial remodeling and the pathogenesis of AF. Targeting the CXCL1–ERS–TXNDC5 axis may offer a novel therapeutic approach for preventing and treating AF-related atrial fibrosis.
心房纤维化是心房颤动（AF）的关键结构底物。本研究旨在探讨趋化因子C-X-C motif Ligand 1 （CXCL1）的促纤维化作用，并阐明内质网应激（ERS）和ER-resident protein thioredoxin domain containing protein 5 （TXNDC5）在这一过程中的作用。方法测定房颤患者和健康对照者血清CXCL1浓度。采用离体大鼠心房组织培养法评价CXCL1对心房纤维化的影响。此外，在原代大鼠心脏成纤维细胞中评估CXCL1对胶原合成、ERS激活和TXNDC5表达的影响。利用ERS的药理抑制和TXNDC5的基因沉默来解释其潜在的机制。结果与对照组相比，AF患者的CXCL1水平升高。在离体大鼠心房组织中，CXCL1处理诱导显著纤维化，上调ERS标记物GRP78和ATF6以及TXNDC5的表达。在心脏成纤维细胞中，CXCL1促进胶原I、胶原III和TGF-β1的分泌。值得注意的是，ERS抑制和TXNDC5敲低均能有效减弱cxcl1诱导的成纤维细胞活化和细胞外基质蛋白表达。结论CXCL1通过激活ERS和上调TXNDC5促进心房纤维化，可能参与心房重构和房颤发病机制，靶向CXCL1 - ERS - TXNDC5轴可能为预防和治疗房颤相关心房纤维化提供新的治疗途径。
{"title":"CXCL1 Promotes Fibrotic Remodeling in Atrial Fibrillation via Activation of TXNDC5 and Endoplasmic Reticulum Stress","authors":"Ran Yin, Cheng-Long Wu, Si-Yang Yu, Kun Huang, Yuan Wen, Jun-Gang Nie, Ru Ying","doi":"10.1155/cdr/7892499","DOIUrl":"https://doi.org/10.1155/cdr/7892499","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Atrial fibrosis is a key structural substrate in atrial fibrillation (AF). This work was conducted to investigate the profibrotic effects of chemokine C-X-C motif Ligand 1 (CXCL1) and elucidate the actions of endoplasmic reticulum stress (ERS) and ER-resident protein thioredoxin domain-containing Protein 5 (TXNDC5) in this process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Serum CXCL1 concentrations were measured in patients with AF and healthy controls. The effects of CXCL1 on atrial fibrosis were evaluated using ex vivo rat atrial tissue culture. Additionally, the influence of CXCL1 on collagen synthesis, ERS activation, and TXNDC5 expression was assessed in primary rat cardiac fibroblasts. Pharmacological inhibition of ERS and gene silencing of TXNDC5 were employed to decipher underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CXCL1 levels were elevated in patients with AF compared to controls. In ex vivo rat atrial tissue, CXCL1 treatment induced marked fibrosis and upregulated the expression of ERS markers GRP78 and ATF6, as well as TXNDC5. In cardiac fibroblasts, CXCL1 promoted the secretion of Collagen I, Collagen III, and TGF-<i>β</i>1. Notably, both ERS inhibition and TXNDC5 knockdown effectively attenuated CXCL1-induced fibroblast activation and extracellular matrix protein expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CXCL1 promotes atrial fibrosis through the activation of ERS and upregulation of TXNDC5, potentially contributing to atrial remodeling and the pathogenesis of AF. Targeting the CXCL1–ERS–TXNDC5 axis may offer a novel therapeutic approach for preventing and treating AF-related atrial fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/7892499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145406707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study investigated the impact of pathological differences between aortic stenosis (AS) and aortic regurgitation (AR) on hemodynamic outcomes following transcatheter aortic valve replacement (TAVR), with a focus on the performance of self-expanding valves relative to annular anatomy.
Methods
In this single-center, retrospective study, patients undergoing TAVR for AS or AR were stratified by annulus area into smaller (< 430 cm2) and larger (≥ 430 cm2) subgroups. Valve sizing was based on annular dimensions (≥ 27 mm for AR/smaller annulus; < 27 mm for AS subgroups). Hemodynamic parameters (aortic valve area [AVA], pressure gradients, and velocity) and prosthesis characteristics (sheath size and compression ratio) were evaluated pre- and postoperatively, with 1-year follow-up.
Results
The AR group required larger sheaths (p = 0.006) and demonstrated superior hemodynamics compared to the AS group: larger postoperative AVA (3.0 ± 0.4 vs. 2.2 ± 0.5 and 2.1 ± 0.6 cm2 in larger and smaller annuli, respectively, p < 0.001); lower maximum (9.7 ± 4.3 vs. 15.8 ± 9.2 and 18.8 ± 10.8 mmHg in larger and smaller annuli, respectively, p < 0.001) and mean gradients (7.8 ± 4.4 mmHg vs. others, p < 0.001); and reduced aortic velocity (1.60 ± 0.43 vs. others, p = 0.038). Smaller annuli exhibited higher prosthesis compression (0.88 ± 0.04 vs. 0.84 ± 0.04 in AR and 0.8 ± 0.06 in larger annulus, p < 0.001), with 20% (n = 8) developing elevated transvalvular gradients (> 20 mmHg) at follow-up.
Conclusions
One-year outcomes revealed distinct hemodynamic profiles post-TAVR between AR and AS groups based on annular size. Patients with AR exhibited more favorable valve performance, supporting TAVR in younger, low-risk patients with AR who have suitable annular anatomy.
{"title":"Hemodynamic Variability in Aortic Stenosis and Regurgitation During Transcatheter Aortic Valve Replacement With Self-Expanding Valves","authors":"Mingfei Li, Jianing Fan, Shasha Chen, Dawei Lin, Xiaochun Zhang, Wenzhi Pan, Daxin Zhou, Junbo Ge","doi":"10.1155/cdr/8821435","DOIUrl":"https://doi.org/10.1155/cdr/8821435","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study investigated the impact of pathological differences between aortic stenosis (AS) and aortic regurgitation (AR) on hemodynamic outcomes following transcatheter aortic valve replacement (TAVR), with a focus on the performance of self-expanding valves relative to annular anatomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this single-center, retrospective study, patients undergoing TAVR for AS or AR were stratified by annulus area into smaller (< 430 cm<sup>2</sup>) and larger (≥ 430 cm<sup>2</sup>) subgroups. Valve sizing was based on annular dimensions (≥ 27 mm for AR/smaller annulus; < 27 mm for AS subgroups). Hemodynamic parameters (aortic valve area [AVA], pressure gradients, and velocity) and prosthesis characteristics (sheath size and compression ratio) were evaluated pre- and postoperatively, with 1-year follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The AR group required larger sheaths (<i>p</i> = 0.006) and demonstrated superior hemodynamics compared to the AS group: larger postoperative AVA (3.0 ± 0.4 vs. 2.2 ± 0.5 and 2.1 ± 0.6 cm<sup>2</sup> in larger and smaller annuli, respectively, <i>p</i> < 0.001); lower maximum (9.7 ± 4.3 vs. 15.8 ± 9.2 and 18.8 ± 10.8 mmHg in larger and smaller annuli, respectively, <i>p</i> < 0.001) and mean gradients (7.8 ± 4.4 mmHg vs. others, <i>p</i> < 0.001); and reduced aortic velocity (1.60 ± 0.43 vs. others, <i>p</i> = 0.038). Smaller annuli exhibited higher prosthesis compression (0.88 ± 0.04 vs. 0.84 ± 0.04 in AR and 0.8 ± 0.06 in larger annulus, <i>p</i> < 0.001), with 20% (<i>n</i> = 8) developing elevated transvalvular gradients (> 20 mmHg) at follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>One-year outcomes revealed distinct hemodynamic profiles post-TAVR between AR and AS groups based on annular size. Patients with AR exhibited more favorable valve performance, supporting TAVR in younger, low-risk patients with AR who have suitable annular anatomy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/8821435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145366846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kritick Bhandari, Maria Qadri, Rochak Dhakal, Sagun Ghimire, Gyanendra Jora, Santosh Basyal, Sanjit Kumar Shah
<div> <section> <h3> Background</h3> <p>Heart failure is a major global health burden associated with high morbidity and mortality. Elevated pulmonary artery pressures (PAP) are linked to worse outcomes in heart failure patients. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, initially developed for diabetes, have demonstrated cardiovascular benefits, but their specific effects on pulmonary hemodynamics remain unclear.</p> </section> <section> <h3> Methods</h3> <p>This systematic review analyzed randomized controlled trials and observational cohort studies evaluating the effects of SGLT2 inhibitors on mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP) in heart failure patients. A comprehensive search of PubMed, Embase, Cochrane Library, and Scopus databases was conducted until August 2024. Studies were appraised using PRISMA and AMSTAR guidelines, the Cochrane bias tool, and the Newcastle–Ottawa Scale.</p> </section> <section> <h3> Hypothesis</h3> <p>SGLT2 inhibitors reduce PAPs in heart failure patients, leading to beneficial pulmonary hemodynamic effects.</p> </section> <section> <h3> Results</h3> <p>Six studies (four RCTs and two observational; <i>n</i> = 346) were included. At rest, pooled analysis of three trials showed a significant reduction in mPAP (MD −1.41 mmHg; 95% CI −2.80 to −0.01; <i>p</i> = 0.05; <i>I</i><sup>2</sup> = 12<i>%</i>). During exercise, two studies demonstrated a nonsignificant reduction in mPAP (MD −3.12 mmHg; 95% CI −7.60 to 1.36; <i>p</i> = 0.17; <i>I</i><sup>2</sup> = 54<i>%</i>). For PASP, pooled analysis of four studies suggested a nonsignificant reduction (MD −6.72 mmHg; 95% CI −14.98 to 1.54; <i>p</i> = 0.11; <i>I</i><sup>2</sup> = 96<i>%</i>), but sensitivity analysis excluding one outlier yielded a significant effect (MD −2.76 mmHg; 95% CI −4.99 to −0.53; <i>p</i> = 0.02; <i>I</i><sup>2</sup> = 0<i>%</i>). Secondary outcomes included significant reductions in PCWP, PADP, and NT-proBNP.</p> </section> <section> <h3> Conclusion</h3> <p>SGLT2 inhibitors demonstrate beneficial effects on pulmonary pressures and hemodynamics in patients with heart failure, with consistent trends toward lower mPAP, PASP, and PCWP. Although results are influenced by study heterogeneity, the overall evidence suggests meaningful hemodynamic improvements. Larger, long-term randomized trials are warranted to clarify subgroup effects (HFrEF vs. HFpEF and dapagliflozin vs. empagliflozin) and establish clinical implica
背景：心力衰竭是与高发病率和高死亡率相关的主要全球健康负担。肺动脉压（PAP）升高与心力衰竭患者预后较差有关。钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂最初是为糖尿病开发的，已经证明对心血管有益，但它们对肺血流动力学的具体影响尚不清楚。方法本系统综述分析了随机对照试验和观察性队列研究，评估SGLT2抑制剂对心力衰竭患者平均肺动脉压（mPAP）和肺动脉收缩压（PASP）的影响。对PubMed、Embase、Cochrane Library和Scopus数据库进行了全面的检索，直到2024年8月。采用PRISMA和AMSTAR指南、Cochrane偏倚工具和Newcastle-Ottawa量表对研究进行评价。假设SGLT2抑制剂降低心力衰竭患者的pap，导致有益的肺血流动力学作用。结果共纳入6项研究（4项rct和2项观察性研究，n = 346）。其余，三个试验的合并分析显示mPAP显著降低（MD - 1.41 mmHg; 95% CI - 2.80至- 0.01;p = 0.05; I2 = 12%）。在运动期间，两项研究显示mPAP无显著降低（MD - 3.12 mmHg; 95% CI - 7.60 ~ 1.36; p = 0.17; I2 = 54%）。对于PASP，四项研究的汇总分析显示无显著降低（MD - 6.72 mmHg; 95% CI - 14.98至1.54;p = 0.11; I2 = 96%），但排除一个异常值的敏感性分析显示有显著效果（MD - 2.76 mmHg; 95% CI - 4.99至- 0.53;p = 0.02; I2 = 0%）。次要结局包括PCWP、PADP和NT-proBNP显著降低。结论SGLT2抑制剂对心力衰竭患者的肺动脉压和血流动力学有有益的影响，并具有降低mPAP、PASP和PCWP的趋势。虽然结果受到研究异质性的影响，但总体证据表明有意义的血流动力学改善。需要更大规模的长期随机试验来澄清亚组效应（HFrEF vs. HFpEF，达格列净vs.恩格列净）并确定临床意义。
{"title":"The Impact of SGLT2 Inhibitors on Pulmonary Artery Pressures and Pulmonary Hemodynamics in Patients With Heart Failure: A Systematic Review","authors":"Kritick Bhandari, Maria Qadri, Rochak Dhakal, Sagun Ghimire, Gyanendra Jora, Santosh Basyal, Sanjit Kumar Shah","doi":"10.1155/cdr/6649731","DOIUrl":"https://doi.org/10.1155/cdr/6649731","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Heart failure is a major global health burden associated with high morbidity and mortality. Elevated pulmonary artery pressures (PAP) are linked to worse outcomes in heart failure patients. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, initially developed for diabetes, have demonstrated cardiovascular benefits, but their specific effects on pulmonary hemodynamics remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This systematic review analyzed randomized controlled trials and observational cohort studies evaluating the effects of SGLT2 inhibitors on mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP) in heart failure patients. A comprehensive search of PubMed, Embase, Cochrane Library, and Scopus databases was conducted until August 2024. Studies were appraised using PRISMA and AMSTAR guidelines, the Cochrane bias tool, and the Newcastle–Ottawa Scale.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Hypothesis</h3>\u0000 \u0000 <p>SGLT2 inhibitors reduce PAPs in heart failure patients, leading to beneficial pulmonary hemodynamic effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six studies (four RCTs and two observational; <i>n</i> = 346) were included. At rest, pooled analysis of three trials showed a significant reduction in mPAP (MD −1.41 mmHg; 95% CI −2.80 to −0.01; <i>p</i> = 0.05; <i>I</i><sup>2</sup> = 12<i>%</i>). During exercise, two studies demonstrated a nonsignificant reduction in mPAP (MD −3.12 mmHg; 95% CI −7.60 to 1.36; <i>p</i> = 0.17; <i>I</i><sup>2</sup> = 54<i>%</i>). For PASP, pooled analysis of four studies suggested a nonsignificant reduction (MD −6.72 mmHg; 95% CI −14.98 to 1.54; <i>p</i> = 0.11; <i>I</i><sup>2</sup> = 96<i>%</i>), but sensitivity analysis excluding one outlier yielded a significant effect (MD −2.76 mmHg; 95% CI −4.99 to −0.53; <i>p</i> = 0.02; <i>I</i><sup>2</sup> = 0<i>%</i>). Secondary outcomes included significant reductions in PCWP, PADP, and NT-proBNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SGLT2 inhibitors demonstrate beneficial effects on pulmonary pressures and hemodynamics in patients with heart failure, with consistent trends toward lower mPAP, PASP, and PCWP. Although results are influenced by study heterogeneity, the overall evidence suggests meaningful hemodynamic improvements. Larger, long-term randomized trials are warranted to clarify subgroup effects (HFrEF vs. HFpEF and dapagliflozin vs. empagliflozin) and establish clinical implica","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/6649731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145366286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Srdjan Babic, Jovan Petrovic, Masa Petrovic, Slobodan Pesic, Slobodan Tanaskovic, Ana Cvetkovic, Predrag Gajin, Nenad Ilijevski
Introduction
This study is aimed at investigating the safety of endovenous laser ablation treatment in the superficial venous system and perforator venous system in patients with previous deep vein thrombosis.
Methods
From February 2017 to January 2023, 28 patients (20 women) with an average age of 41.5 ± 8.6 years, insufficient great saphenous vein and previous deep vein thrombosis were treated. All patients were diagnosed based on previous ultrasound examinations. In this retrospective study, patients were indeed included if they met specific criteria. Preoperative evaluations and thrombophilia assessments were conducted.
Results
Most patients had previous thrombosis in the popliteal vein (36.4%), while 31.8% had thrombosis in both the femoral and calf veins. Technical success was achieved in all patients, with concomitant procedures (closure of incompetent perforators and phlebectomies), and during follow-up (20 ± 16 months, range: 2–168 months), there were no signs of recanalisation of previously treated superficial veins. Patients were followed up at 1-month, 3-month, 6-month and 12-month intervals postprocedure. Recurrent deep vein thrombosis occurred in two (7%) patients after 26 and 31 months after treatment. Early complications included one (3.5%) case of endovenous heat-induced thrombosis Type II.
Conclusions
Endovenous laser ablation is safe and effective in patients with resolved deep vein thrombosis when combined with appropriate anticoagulant therapy.
{"title":"Endovenous Laser Ablation of Insufficient Superficial Veins in Patients After Deep Vein Thrombosis Recanalisation","authors":"Srdjan Babic, Jovan Petrovic, Masa Petrovic, Slobodan Pesic, Slobodan Tanaskovic, Ana Cvetkovic, Predrag Gajin, Nenad Ilijevski","doi":"10.1155/cdr/8458282","DOIUrl":"https://doi.org/10.1155/cdr/8458282","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This study is aimed at investigating the safety of endovenous laser ablation treatment in the superficial venous system and perforator venous system in patients with previous deep vein thrombosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From February 2017 to January 2023, 28 patients (20 women) with an average age of 41.5 ± 8.6 years, insufficient great saphenous vein and previous deep vein thrombosis were treated. All patients were diagnosed based on previous ultrasound examinations. In this retrospective study, patients were indeed included if they met specific criteria. Preoperative evaluations and thrombophilia assessments were conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most patients had previous thrombosis in the popliteal vein (36.4%), while 31.8% had thrombosis in both the femoral and calf veins. Technical success was achieved in all patients, with concomitant procedures (closure of incompetent perforators and phlebectomies), and during follow-up (20 ± 16 months, range: 2–168 months), there were no signs of recanalisation of previously treated superficial veins. Patients were followed up at 1-month, 3-month, 6-month and 12-month intervals postprocedure. Recurrent deep vein thrombosis occurred in two (7%) patients after 26 and 31 months after treatment. Early complications included one (3.5%) case of endovenous heat-induced thrombosis Type II.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Endovenous laser ablation is safe and effective in patients with resolved deep vein thrombosis when combined with appropriate anticoagulant therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/8458282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145316952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingfei Li, Dawei Lin, Lei Zhang, Jianing Fan, Wenzhi Pan, Xiaochun Zhang, Daxin Zhou, Junbo Ge
Objectives
This study was aimed at evaluating the effectiveness of fluoroscopy as an intraprocedural guidance method during left atrial appendage occlusion (LAAO) using the LACbes device.
Methods
The study included a cohort of 477 patients with nonvalvular atrial fibrillation (AF) who underwent LAAO. The cohort was divided into two groups: a retrospective group of 240 patients who underwent standard procedures involving both transesophageal echocardiogram (TEE) and fluoroscopy and a prospective group of 237 patients who only underwent fluoroscopy. The retrospective cohort was analyzed for device positioning, anchoring, compression, and peridevice leak (PDL) using both TEE and fluoroscopy to provide detailed insights for potential application in the prospective cohort. Clinical outcomes were compared between the two groups.
Results
There were no significant differences in left atrial appendage (LAA) characteristics and other echocardiographic parameters between the two groups. Although the prospective group had a higher prevalence of implantation failure and more deployment attempts per procedure, these differences did not reach statistical significance. Notable differences were observed in fluoroscopy and operation times. Specifically, the prospective group had longer fluoroscopy times and more deployment attempts per procedure but shorter overall operation times compared to the retrospective group. Additionally, patients in the prospective group had shorter hospital stays and lower hospitalization costs. Periprocedural and 2-year follow-up complications were comparable between both cohorts, with no statistically significant differences observed in pericardial effusion, peripheral vascular complications, survival, cardiac death, PDL, or device thrombus.
Conclusions
The use of fluoroscopy as the sole guidance modality for LAAO with the LACbes device demonstrated promising results in terms of efficacy and safety. It emerges as a viable and cost-effective alternative, offering a more efficient approach for LAAO.
{"title":"Single Fluoroscopy Versus Transesophageal Echocardiogram: A Comparative Evaluation for Left Atrial Appendage Occlusion With LACbes Device","authors":"Mingfei Li, Dawei Lin, Lei Zhang, Jianing Fan, Wenzhi Pan, Xiaochun Zhang, Daxin Zhou, Junbo Ge","doi":"10.1155/cdr/9933780","DOIUrl":"https://doi.org/10.1155/cdr/9933780","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study was aimed at evaluating the effectiveness of fluoroscopy as an intraprocedural guidance method during left atrial appendage occlusion (LAAO) using the LACbes device.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included a cohort of 477 patients with nonvalvular atrial fibrillation (AF) who underwent LAAO. The cohort was divided into two groups: a retrospective group of 240 patients who underwent standard procedures involving both transesophageal echocardiogram (TEE) and fluoroscopy and a prospective group of 237 patients who only underwent fluoroscopy. The retrospective cohort was analyzed for device positioning, anchoring, compression, and peridevice leak (PDL) using both TEE and fluoroscopy to provide detailed insights for potential application in the prospective cohort. Clinical outcomes were compared between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were no significant differences in left atrial appendage (LAA) characteristics and other echocardiographic parameters between the two groups. Although the prospective group had a higher prevalence of implantation failure and more deployment attempts per procedure, these differences did not reach statistical significance. Notable differences were observed in fluoroscopy and operation times. Specifically, the prospective group had longer fluoroscopy times and more deployment attempts per procedure but shorter overall operation times compared to the retrospective group. Additionally, patients in the prospective group had shorter hospital stays and lower hospitalization costs. Periprocedural and 2-year follow-up complications were comparable between both cohorts, with no statistically significant differences observed in pericardial effusion, peripheral vascular complications, survival, cardiac death, PDL, or device thrombus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The use of fluoroscopy as the sole guidance modality for LAAO with the LACbes device demonstrated promising results in terms of efficacy and safety. It emerges as a viable and cost-effective alternative, offering a more efficient approach for LAAO.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/9933780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145316766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biao Hou, Xuejian Hou, Liyue Zhang, Tingting Liu, Yang Li, Ran Dong
Purpose
Myocardial ischemia–reperfusion injury (MIRI) is a condition in which the heart is aggravated when blood flow is restored after tissue damage caused by ischemia. Metformin (Met), a widely prescribed antidiabetic medication, has demonstrated promising cardioprotective properties, particularly through its anti-inflammatory, antiapoptotic, and metabolic regulatory mechanisms. This study investigates the cardioprotective effects of Met in a rat model of MIRI, focusing on its modulation of the c-Jun N-terminal kinase (JNK) pathway and inhibition of PANoptosis mechanisms.
Methods
The proportion of myocardial infarction was determined by triphenyl tetrazole chloride (TTC) staining. Wheat germ agglutinin (WGA) staining is used to determine whether myocardial cells are hypertrophic and other pathological conditions. Serum markers of myocardial injury along with inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence and Western blotting were employed to evaluate myocardial cell PANoptosis and the involvement of the JNK pathway.
Results
After MIRI, TTC staining revealed apparent myocardial infarction, and WGA staining showed significant myocardial cell hypertrophy. There was also a marked increase in myocardial injury markers, inflammatory factors, and reactive oxygen species (ROS). Met significantly reduced the myocardial injury area and notably lowered serum levels of c-TnI, CK-MB, LDH, IL-6, TNF-α, and ROS. Immunofluorescence and Western blot analyses demonstrated that Met attenuates myocardial cell PANoptosis by inhibiting JNK phosphorylation and reducing ROS generation. The cardioprotective effect of Met was reversed by the addition of anisomycin (ANI). The protective effect of JNK-specific inhibitors administered as monotherapy was found to be comparable to that of Met. The aforementioned results suggest that the regulation of the JNK pathway is a critical factor contributing to its protective effect.
Conclusion
The cardioprotective effect of Met in the rat model of MIRI is mediated through the regulation of the JNK pathway and PANoptosis. These findings suggest that Met may provide a potential therapeutic approach for treating MIRI.
心肌缺血再灌注损伤（心肌缺血再灌注损伤，心肌缺血再灌注损伤）是指心肌缺血组织损伤后，血流恢复后心脏功能加重的一种疾病。二甲双胍（Metformin, Met）是一种广泛使用的抗糖尿病药物，已被证明具有良好的心脏保护作用，特别是通过其抗炎、抗细胞凋亡和代谢调节机制。本研究探讨了Met在MIRI大鼠模型中的心脏保护作用，重点研究了其对c-Jun n -末端激酶（JNK）通路的调节和对PANoptosis的抑制机制。方法采用氯化三苯四唑（TTC）染色法测定心肌梗死比例。小麦胚芽凝集素（WGA）染色用于确定心肌细胞是否肥厚及其他病理状况。采用酶联免疫吸附法（ELISA）检测心肌损伤血清标志物及炎症因子水平。采用免疫荧光和Western blotting检测心肌细胞PANoptosis及JNK通路的参与情况。结果MIRI后，TTC染色显示明显心肌梗死，WGA染色显示心肌细胞明显肥大。心肌损伤标志物、炎症因子和活性氧（ROS）也明显增加。蛋氨酸显著减少心肌损伤面积，显著降低血清c-TnI、CK-MB、LDH、IL-6、TNF-α、ROS水平。免疫荧光和Western blot分析表明，Met通过抑制JNK磷酸化和减少ROS生成来减轻心肌细胞PANoptosis。加入大霉素（ANI）后，Met的心脏保护作用被逆转。jnk特异性抑制剂作为单药治疗的保护作用被发现与Met相当。上述结果提示，JNK通路的调控是其发挥保护作用的关键因素。结论Met在MIRI大鼠模型中的心脏保护作用是通过调控JNK通路和PANoptosis介导的。这些发现表明Met可能为治疗MIRI提供一种潜在的治疗方法。
{"title":"Metformin Attenuates Myocardial Ischemia–Reperfusion Injury in Rats by Modulating JNK Pathway and Inhibiting PANoptosis Mechanisms","authors":"Biao Hou, Xuejian Hou, Liyue Zhang, Tingting Liu, Yang Li, Ran Dong","doi":"10.1155/cdr/4642838","DOIUrl":"https://doi.org/10.1155/cdr/4642838","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Myocardial ischemia–reperfusion injury (MIRI) is a condition in which the heart is aggravated when blood flow is restored after tissue damage caused by ischemia. Metformin (Met), a widely prescribed antidiabetic medication, has demonstrated promising cardioprotective properties, particularly through its anti-inflammatory, antiapoptotic, and metabolic regulatory mechanisms. This study investigates the cardioprotective effects of Met in a rat model of MIRI, focusing on its modulation of the c-Jun N-terminal kinase (JNK) pathway and inhibition of PANoptosis mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The proportion of myocardial infarction was determined by triphenyl tetrazole chloride (TTC) staining. Wheat germ agglutinin (WGA) staining is used to determine whether myocardial cells are hypertrophic and other pathological conditions. Serum markers of myocardial injury along with inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence and Western blotting were employed to evaluate myocardial cell PANoptosis and the involvement of the JNK pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After MIRI, TTC staining revealed apparent myocardial infarction, and WGA staining showed significant myocardial cell hypertrophy. There was also a marked increase in myocardial injury markers, inflammatory factors, and reactive oxygen species (ROS). Met significantly reduced the myocardial injury area and notably lowered serum levels of c-TnI, CK-MB, LDH, IL-6, TNF-<i>α</i>, and ROS. Immunofluorescence and Western blot analyses demonstrated that Met attenuates myocardial cell PANoptosis by inhibiting JNK phosphorylation and reducing ROS generation. The cardioprotective effect of Met was reversed by the addition of anisomycin (ANI). The protective effect of JNK-specific inhibitors administered as monotherapy was found to be comparable to that of Met. The aforementioned results suggest that the regulation of the JNK pathway is a critical factor contributing to its protective effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The cardioprotective effect of Met in the rat model of MIRI is mediated through the regulation of the JNK pathway and PANoptosis. These findings suggest that Met may provide a potential therapeutic approach for treating MIRI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/4642838","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoya Chen, Juan Yang, Ling Xu, Fang Yin, Jihan Huang, Yinghua Lv, Qingshan Zheng, Lujin Li
Objective
The aim of this study was to establish a placebo response model for efficacy indicators in heart failure with preserved ejection fraction (HFpEF) clinical trials, facilitating sample size estimation and trial optimization.
Methods
PubMed, EMBASE, and Cochrane Library databases were searched systematically for placebo-controlled trials of HFpEF up to May 26, 2024. Using model-based meta-analysis (MBMA), we analyzed cardiovascular death or heart failure hospitalization, cardiovascular death, heart failure hospitalization, all causes of death, and changes from baseline in the 6-min walk distance (6MWD) of the placebo group. The final model simulated the placebo effect distribution for these indicators under varying scenarios.
Results
A total of 29 studies and 14,302 participants were analyzed. A log-normal risk function was developed to describe four event rate indicators, and typical event rates for the placebo group over 6 years were simulated. After 1 year, rates for cardiovascular death or heart failure hospitalization (composite event), heart failure hospitalization, all causes of death, and cardiovascular death were 11.1%, 10.5%, 2.91%, and 2.33%, respectively. We used a linear model to describe the time–effect relationship of the change value of change from baseline in 6MWD, revealing typical changes at 1, 3, and 6 months as 1.47, 4.76, and 9.57 m, respectively. These values indicated that using the composite event as criteria could reduce the sample size by 500–12,000 cases, while 548 cases were sufficient for changes in 6MWD. The placebo effect model was also used as an external control in evaluating Sacubitril/Valsartan and exercise training efficacy.
Conclusion
This placebo response model provides essential support for sample size estimation, trial optimization, and drug efficacy evaluation in future HFpEF clinical trials.
{"title":"Optimization of Clinical Trial Design and Decision-Making for Heart Failure with Preserved Ejection Fraction (HFpEF): A Meta-Analysis Based on a Placebo Response Model","authors":"Xiaoya Chen, Juan Yang, Ling Xu, Fang Yin, Jihan Huang, Yinghua Lv, Qingshan Zheng, Lujin Li","doi":"10.1155/cdr/7087720","DOIUrl":"https://doi.org/10.1155/cdr/7087720","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to establish a placebo response model for efficacy indicators in heart failure with preserved ejection fraction (HFpEF) clinical trials, facilitating sample size estimation and trial optimization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, EMBASE, and Cochrane Library databases were searched systematically for placebo-controlled trials of HFpEF up to May 26, 2024. Using model-based meta-analysis (MBMA), we analyzed cardiovascular death or heart failure hospitalization, cardiovascular death, heart failure hospitalization, all causes of death, and changes from baseline in the 6-min walk distance (6MWD) of the placebo group. The final model simulated the placebo effect distribution for these indicators under varying scenarios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 29 studies and 14,302 participants were analyzed. A log-normal risk function was developed to describe four event rate indicators, and typical event rates for the placebo group over 6 years were simulated. After 1 year, rates for cardiovascular death or heart failure hospitalization (composite event), heart failure hospitalization, all causes of death, and cardiovascular death were 11.1%, 10.5%, 2.91%, and 2.33%, respectively. We used a linear model to describe the time–effect relationship of the change value of change from baseline in 6MWD, revealing typical changes at 1, 3, and 6 months as 1.47, 4.76, and 9.57 m, respectively. These values indicated that using the composite event as criteria could reduce the sample size by 500–12,000 cases, while 548 cases were sufficient for changes in 6MWD. The placebo effect model was also used as an external control in evaluating Sacubitril/Valsartan and exercise training efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This placebo response model provides essential support for sample size estimation, trial optimization, and drug efficacy evaluation in future HFpEF clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/7087720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Delin Li, Hui Li, Quanwei Zhao, Caiwei Gong, Long Chen, Chengzhu Xiong, Shaoliang Shen, Fujun Liao, Wupeng Liu, Danan Liu
Objective
The current study is aimed at elucidating the mechanisms underlying the involvement of ferroptosis in atherosclerosis (AS) and exploring potential therapeutic targets.
Methods
Endothelial function and lipid peroxidation were assessed in vitro using HCAECs treated with OX-LDL. SLC7A11, GPX4, TfR1, and FTH1 were analyzed by western blot, respectively. Representative markers of ferroptosis including LDH, MDA, 4-HNE, GSH, and iron content were detected. HTR2B miRNA (OE-HTR2B) and controls (OE-NC, empty vector) were transfected. AS was induced in ApoE-/- mice through a high-fat diet. The effect of ferroptosis inhibition on atherosclerotic lesion development was evaluated by different inhibitor treatments.
Results
RNA-Seq analysis revealed dysregulated HTR2B expression in HCAECs exposed to OX-LDL, indicating its involvement in AS pathogenesis. OX-LDL exposure reduced cell viability and induced ferroptosis, characterized by decreased SLC7A11 and GPX4 expression and increased lipid peroxidation. Overexpression of HTR2B rescued cell viability, reduced Fe2+ accumulation, and upregulated SLC7A11 and GPX4, suggesting a protective role against ferroptosis. Further, HTR2B regulated ferroptosis via the PI3K/AKT pathway, as evidenced by changes in pathway protein phosphorylation. By activating HTR2B with an agonist BW-723C86, we verified that HTR2B can inhibit ferroptosis through the PI3K/AKT pathway in an atherosclerotic mouse model.
Conclusion
HTR2B suppressed ferroptosis by promoting the PI3K/AKT axis, enhanced cellular viability, and exhibited a protective role in AS.
{"title":"HTR2B-Mediated Endothelial Protection: Modulating Ferroptosis via the PI3K/AKT Signaling Pathway in Atherosclerosis","authors":"Delin Li, Hui Li, Quanwei Zhao, Caiwei Gong, Long Chen, Chengzhu Xiong, Shaoliang Shen, Fujun Liao, Wupeng Liu, Danan Liu","doi":"10.1155/cdr/7934590","DOIUrl":"https://doi.org/10.1155/cdr/7934590","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The current study is aimed at elucidating the mechanisms underlying the involvement of ferroptosis in atherosclerosis (AS) and exploring potential therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Endothelial function and lipid peroxidation were assessed in vitro using HCAECs treated with OX-LDL. SLC7A11, GPX4, TfR1, and FTH1 were analyzed by western blot, respectively. Representative markers of ferroptosis including LDH, MDA, 4-HNE, GSH, and iron content were detected. HTR2B miRNA (OE-HTR2B) and controls (OE-NC, empty vector) were transfected. AS was induced in ApoE<sup>-/-</sup> mice through a high-fat diet. The effect of ferroptosis inhibition on atherosclerotic lesion development was evaluated by different inhibitor treatments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RNA-Seq analysis revealed dysregulated <i>HTR2B</i> expression in HCAECs exposed to OX-LDL, indicating its involvement in AS pathogenesis. OX-LDL exposure reduced cell viability and induced ferroptosis, characterized by decreased SLC7A11 and GPX4 expression and increased lipid peroxidation. Overexpression of <i>HTR2B</i> rescued cell viability, reduced Fe<sup>2+</sup> accumulation, and upregulated SLC7A11 and GPX4, suggesting a protective role against ferroptosis. Further, <i>HTR2B</i> regulated ferroptosis via the PI3K/AKT pathway, as evidenced by changes in pathway protein phosphorylation. By activating HTR2B with an agonist BW-723C86, we verified that <i>HTR2B</i> can inhibit ferroptosis through the PI3K/AKT pathway in an atherosclerotic mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HTR2B suppressed ferroptosis by promoting the PI3K/AKT axis, enhanced cellular viability, and exhibited a protective role in AS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/7934590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145223804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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