Cardiovascular Drugs and Therapy最新文献

{"title":"Calcium Signaling in Cardiac Fibroblasts: Roles in Fibrosis and Therapeutic Implications.","authors":"Naim Kittana","doi":"10.1007/s10557-025-07699-w","DOIUrl":"https://doi.org/10.1007/s10557-025-07699-w","url":null,"abstract":"<p><strong>Background: </strong>Cardiac fibroblasts (CFs) are numerically a highly abundant cell type in the heart and are responsible for the homeostasis of the extracellular matrix (ECM) in the myocardium under normal conditions. Upon cardiac stress, these cells become activated and transdifferentiate into myofibroblasts (MyCFs), which are characterized by their increased capacity to proliferate, migrate, and secrete ECM components and bioactive molecules. The trans-differentiation of CFs is induced by several factors like angiotensin II (Ang II) and transforming growth factor-ß (TGF-ß and is crucial in cardiac remodeling. In recent years, signal mechanisms playing a role in MyCFs behavior have been intensively investigated, including the role of the universal second messenger calcium (Ca²⁺).</p><p><strong>Aims and scope: </strong>Here, we review the current knowledge on Ca²⁺ handling and Ca²⁺-dependent signal transduction in cardiac (myo)fibroblasts, with a focus on the mechanisms leading to intracellular Ca²⁺ release and Ca²⁺ entry from the extracellular space, which is involved in the generation of Ca²⁺ transients and regulation of Ca²⁺ oscillation. Moreover, the activation of Ca²⁺-induced signal transduction involving different kinases and the phosphatase calcineurin in CFs is described.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Angiotensin Receptor-Neprilysin Inhibitors Use and Better Cardiorenal Outcomes in Patients With Heart Failure and Acute Kidney Disease.","authors":"Jui-Yi Chen, Heng-Chih Pan, Vin-Cent Wu","doi":"10.1007/s10557-025-07698-x","DOIUrl":"https://doi.org/10.1007/s10557-025-07698-x","url":null,"abstract":"<p><strong>Purpose: </strong>Angiotensin receptor-neprilysin inhibitors (ARNi) have been shown to improve cardiovascular outcomes in heart failure (HF) patients. However, their impact on HF patients with concurrent acute kidney disease (AKD) remains underexplored. This study investigated the outcomes of ARNi compared to angiotensin-converting enzyme inhibitors (ACEi) in HF patients with AKD.</p><p><strong>Methods: </strong>The study included 20,009 hospitalized HF and AKD patients who underwent dialysis during hospitalization, recovered from dialysis within 90 days after discharge, and were followed until November 30, 2022, using data from TriNetX. The study period began in July 2015, coinciding with the availability of ARNi in the market. Propensity score matching (1:1) was applied to balance ARNi and ACEi groups. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were calculated to assess the risks of mortality, major adverse kidney events (MAKE), readmission and major adverse cardiac events (MACE). The follow-up period was conducted with a maximum duration of 5 years.</p><p><strong>Results: </strong>A total of 20,009 AKD patients (mean [SD] age, 59.1 [12.2] years) were enrolled, of whom 21.9% received ARNi, with a median follow-up of 2.3 years. After matching, 4391 patients (mean age, 58.6 years; male, 67.9%) were identified in both the ARNi and control groups. ARNi users exhibited a significantly lower risk of mortality (aHR, 0.32, 95% CI 0.13-0.80, p = 0.01), MAKE (aHR, 0.58, 95% CI 0.51-0.66, p < 0.01 ), and readmission (aHR, 0.61, 95% CI 0.55-0.68, p <0.01) versus controls. However, no significant difference in the risk of MACE was observed between the two groups (aHR, 0.94, 95% CI 0.82-1.09, p = 0.78). Subgroup analysis revealed ARNi users, when concomitantly treated with mineralocorticoids, diuretics, or beta-blockers had significantly lower risks of mortality, readmission, and MAKE than the control group. In addition, ARNi significantly reduced mortality and MAKE in patients with GFR 30-60 mL/min/1.73 m², irrespective of proteinuria status. However, no significant benefit was observed in patients with GFR <30 mL/min/1.73 m².</p><p><strong>Conclusions: </strong>In HF patients with AKD, ARNi was associated with reduced all-cause mortality, MAKE, and readmission risks compared to ACEi, particularly with concurrent mineralocorticoids, diuretics, or beta-blockers. Future research is necessary to further investigate the impact of ARNi on outcomes in patients with HF and AKD.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An HDL Cholesterol paradox.","authors":"Sultana Monira Hussain, John J McNeil","doi":"10.1007/s10557-025-07703-3","DOIUrl":"https://doi.org/10.1007/s10557-025-07703-3","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Catheter Ablation and Left Atrial Appendage Occlusion in Atrial Fibrillation: From Data to Clinical Reality.","authors":"Kyriakos Dimitriadis, Eleni Adamopoulou, Nikolaos Pyrpyris, Panagiotis Iliakis, Eirini Beneki, Dimitrios Konstantinidis, Christos Fragkoulis, Alexios Antonopoulos, Aggelos Papanikolaou, Konstantinos Aznaouridis, Konstantina Aggeli, Konstantinos Tsioufis","doi":"10.1007/s10557-025-07685-2","DOIUrl":"https://doi.org/10.1007/s10557-025-07685-2","url":null,"abstract":"<p><strong>Purpose: </strong>Atrial fibrillation (AF) requires treatment that focuses on two main goals: symptom control and prevention of thromboembolic events. Catheter ablation and left atrial appendage occlusion (LAAO) constitute two well-established treatment methods in selected patients that accomplish these two goals correspondingly. Recently, there is increasing interest in performing the two procedures concomitantly in a so-called \"combined\" or \"one-stop\" procedure. This review aims to summarize the current data on the combined procedure, from the rationale and the techniques to its clinical efficacy, indications and future directions.</p><p><strong>Methods: </strong>An extensive search has been conducted using the MEDLINE/PubMed database to identify the relevant studies.</p><p><strong>Results: </strong>The reported success rates of the combined procedure are very high and frequently reach 100% when performed by experienced operators. The periprocedural and follow-up complications are low, the procedure is cost-effective, while there is significant stroke, bleeding and arrhythmia incidence reduction that does not seem to be undermined by interference between the two interventions. There are also a few indications that the one-stop procedure has a positive effect on left atrial mechanical function as it has been correlated with left atrial reverse remodeling. On the other hand, some studies suggest possible increase in peri-device leaks (PDLs), compared with LAAO alone, which could in turn negatively affect the clinical outcomes. Most available studies are small and observational, with a lack of randomized controlled trials.</p><p><strong>Conclusion: </strong>Catheter ablation and left atrial appendage occlusion can be safely and effectively combined in a cost-effective single procedure in carefully selected patients.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opioid-Sparing Effects of Erector Spinae Plane Block in Off-Pump Coronary Artery Bypass Grafting with Median Sternotomy: A Randomized Controlled Trial.","authors":"Yanan Zhang, Jian Liu, Kun Lv, Fei Wang, Yafei Shi, Peijun You, Wenzhu Wang","doi":"10.1007/s10557-025-07697-y","DOIUrl":"https://doi.org/10.1007/s10557-025-07697-y","url":null,"abstract":"<p><strong>Purpose: </strong>This study assessed the efficacy of preoperative erector spinae plane block (ESPB) in reducing intraoperative opioid use and enhancing recovery in off-pump coronary artery bypass grafting (OPCABG) patients, who typically require high-dose opioids with associated postoperative risks.</p><p><strong>Methods: </strong>A prospective, double-blind randomized controlled trial was conducted on 37 patients. Patients were randomized to receive either bilateral ESPB with 0.375% ropivacaine or a sham block with normal saline. Primary outcomes included intraoperative sufentanil consumption, while secondary outcomes encompassed hemodynamic stability, postoperative pain scores, mechanical ventilation (MV) duration, and hospital stay.</p><p><strong>Results: </strong>The ESPB group demonstrated a significant reduction in intraoperative sufentanil consumption compared to the sham group (150.3 ± 36.1 µg vs. 194.4 ± 38.3 µg, p = 0.001). Postoperatively, ESPB patients exhibited lower pain scores at rest and during coughing within the first 6 h post-extubation (p < 0.001) and required less rescue analgesia (5.3% vs. 50.0%, p = 0.003). Additionally, ESPB shortened MV duration (5.43 ± 1.65 h vs. 6.88 ± 1.68 h, p = 0.013). No significant differences were observed in cardiac care unit or hospital stay lengths.</p><p><strong>Conclusion: </strong>Preoperative ESPB effectively reduces intraoperative opioid requirements and provides sustained analgesia in the early postoperative period, facilitating earlier extubation. These findings support ESPB as a valuable component of multimodal analgesia in OPCABG, though further large-scale studies are needed to validate these results and optimize its application.</p><p><strong>Clinical trial registration: </strong>The trial was registered with the China Clinical Trials Center ( http://www.chictr.org.cn , ChiCTR2200066902) on December 21, 2022.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geranylgeranylacetone as Prevention for Postoperative Atrial Fibrillation (GENIALITY).","authors":"Kennedy S Ramos, Soufiane Nassiri, Leonoor F J Wijdeveld, Reinier L van der Palen, Myrthe F Kuipers, Mellanie True Hills, Pieter Slijkerman, Daniel H van Raalte, M Louis Handoko, Natasja M S de Groot, Nimrat Grewal, Robert J M Klautz, Etto C Eringa, Bianca J J M Brundel","doi":"10.1007/s10557-025-07693-2","DOIUrl":"https://doi.org/10.1007/s10557-025-07693-2","url":null,"abstract":"<p><strong>Purpose: </strong>Interestingly, 30-50% of patients undergoing elective cardiothoracic surgery develop postoperative AF (PoAF). Unfortunately, preventive PoAF therapy is still suboptimal. In our previous studies, we showed that oral Geranylgeranylacetone (GGA) administration increased cardioprotective heat shock protein (HSP) protecting against AF onset and progression in clinically relevant animal model studies.</p><p><strong>Methods: </strong>The GENIALITY study is a phase II single-center, double-blind, placebo-controlled randomized trial comparing the efficacy of GGA in preventing PoAF. Participants (N = 146) are adult patients, without any registered history of AF, undergoing elective open-heart surgery for valvular disease, coronary artery bypass grafting, or concomitant, and are allocated with ratio 1:1 in treatment or placebo groups. Daily administration of 300 mg of GGA or placebo starts 5 days before until 3 days after surgery. Cardiac rhythm will be monitored using a Holter monitoring post-surgery until hospital discharge. Additionally, blood samples, right atrial appendage tissue, and epicardial adipose tissue will be collected to assess proteostasis levels.</p><p><strong>Results: </strong>The primary endpoint is the assessment of PoAF incidence in the GGA group compared to the placebo group. Secondary endpoints include the evaluation of HSP levels through biochemical analysis in both blood and atrial tissue.</p><p><strong>Conclusion: </strong>The GENIALITY study aims to reduce PoAF incidence in the GGA group compared to the placebo group. Herewith, we expect to obtain proof of concept for a beneficial effect of GGA in preventing PoAF in patients undergoing cardiothoracic surgery.  TRIAL REGISTRATION: Clinical Trial Information System (CTIS) registry: 2024-514743-28-00. Authorized on September 30th 2024.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Potential Drug Targets in Coronary Atherosclerosis: Insights from the Druggable Genome and Mendelian Randomization.","authors":"Ruikang Liu, Chiyun Sun, Jun Li, Guangyi Yang, Ke Xu, Jiaming Hu, Chao Meng, Xiao Xia, Yonghao Li, Yiying Liu","doi":"10.1007/s10557-025-07694-1","DOIUrl":"https://doi.org/10.1007/s10557-025-07694-1","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to identify therapeutic targets for coronary atherosclerosis (CA) using publicly available datasets while exploring its pathophysiologic mechanisms, mediators and potential side effects.</p><p><strong>Methods: </strong>We conducted a two-sample Mendelian randomization (MR) and single-cell MR analyses integrating identified druggable genes to evaluate the causal relationship between expression quantitative trait loci (eQTL) and CA in both peripheral and central tissues. Using peripheral protein quantitative trait loci (pQTL) data, we further validated the identified targets at the proteomic level through summary data-based MR (SMR) and HEIDI tests. Concurrently, mediation MR analysis was employed to investigate potential mechanistic pathways underlying the role of these targets in CA. Additionally, a phenotype-wide MR (Phe-MR) analysis was performed to explore other potential indications for the therapeutic application of the identified targets.</p><p><strong>Results: </strong>In conclusion, we identified three CA-associated genes in peripheral tissues (VAMP8, MFGE8 and PDGFD) two CA-associated genes in central tissues (GGCX and NPEPPS). In addition, single-cell MR analyses revealed that GGCX was associated with increased CA risk in excitatory, inhibitory and oligodendrocyte precursor cells, whereas NPEPPS was associated with protection in oligodendrocyte lineage cells. Finally, Phe-MR analyses indicated possible indications and side effects of the targets.</p><p><strong>Conclusion: </strong>Our study provides genetic evidence for VAMP8, MFGE8, PDGFD, GGCX and NPEPPS as potential therapeutic targets for CA, highlighting their clinical relevance, associated risks and mediators, and providing valuable insights for the development of novel CA therapeutics.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigation of Injury from Myocardial Infarction by Pentamidine, an Inhibitor of the Acetyltransferase Tip60.","authors":"Xinrui Wang, Katherine R Harty, Tina C Wan, Zhuocheng Qu, Brian C Smith, John W Lough, John A Auchampach","doi":"10.1007/s10557-025-07696-z","DOIUrl":"10.1007/s10557-025-07696-z","url":null,"abstract":"<p><strong>Purpose: </strong>There is an urgent unmet need for new pharmacologic approaches that promote re-muscularization and repair following myocardial infarction (MI). We previously reported that genetic depletion of the acetyltransferase Tip60 after MI in a mouse model activates the CM cell-cycle, reduces scarring, and restores cardiac function, and that these beneficial effects are mimicked by the Tip60-selective inhibitor TH1834. Here, we investigated whether the FDA-approved anti-microbial agent pentamidine, a Tip60 inhibitor from which TH1834 is derived, also protects from the damaging effects of MI.</p><p><strong>Methods: </strong>Adult (10-14 weeks old) C57Bl/6 mice were subjected to permanent left coronary artery ligation to induce MI. Subsequently, echocardiography, electrocardiography, cardiac staining, and molecular analyses were performed to monitor the effects of treatment with pentamidine on cardiac injury and function.</p><p><strong>Results: </strong>We report that transient systemic administration of pentamidine on days 3-16 post-MI at a daily dose of 3 mg/kg efficiently improved cardiac function for up to ten months. This was accompanied by improved survival, diminished scarring, and increased activation of cell-cycle markers in CMs located in the infarct border zone in the absence of hypertrophy. Histological assessments suggested that post-MI treatment with pentamidine reduced site-specific acetylation of the minor histone variant H2A.Z at lysines K4 and K7 in CMs, indicative of the dedifferentiation process which must occur prior to CM proliferation. Treating mice with pentamidine post-MI produced no prominent electrophysiological changes.</p><p><strong>Conclusions: </strong>These findings support the translational potential of pentamidine for treatment of MI, and provide evidence that functional improvement is mediated, in part, by CM renewal due to inhibition of the acetyltransferase activity of Tip60.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions Between Direct Oral Anticoagulants and Drugs Involving CYP-Enzymes and P-gp Transporters Detected by a Clinical Decision Support System: A Retrospective Cohort Study.","authors":"Stephanie C M Wuyts, Sophie Bonte, Naomi Thielemans, Fenne Vandervorst, Berlinde von Kemp, Stephane Steurbaut, Alain G Dupont, Pieter Cornu","doi":"10.1007/s10557-025-07691-4","DOIUrl":"https://doi.org/10.1007/s10557-025-07691-4","url":null,"abstract":"<p><strong>Purpose: </strong>Physicians can be supported by electronic clinical decision support systems (CDSS) for drug-drug interaction (DDI) management of DDIs between direct oral anticoagulants (DOACs) and CYP3 A4/P-glycoprotein (P-gp) inhibitors and inducers, to prevent adverse drug events (ADEs).</p><p><strong>Methods: </strong>A retrospective cohort study was performed studying DDI alerts for DOAC-CYP3 A4/P-gp influencing drug combination prescriptions in patients admitted to a tertiary care hospital. Patient-, DDI-, and ADE-related data were analyzed to explore CDSS performance and real-world DDI management. A multidisciplinary panel conducted an ADE analysis using the Drug Interaction Probability Scale.</p><p><strong>Results: </strong>Out of 15,201 triggered CDS alerts, 166 individual alerts were included. Primary indication for DOAC therapy was atrial fibrillation (86.1%). The most involved DOAC was dabigatran (63%). DDI exposure was median 3 days (IQR = 2-7 days). CYP3 A4/P-gp inhibitor DDIs were most prevalent (n = 121), with amiodarone being most prevalently prescribed (71%). Inducers were mainly antiepileptic drugs (n = 31). Thirty-four CDS alerts (20%) were actively shown to the physician upon prescribing (acceptance rate 50%). Eighteen ADEs were identified (11%, 14 bleeding; 4 thromboembolic events), 15 having a possible and 3 a probable probability of being DDI associated.</p><p><strong>Conclusion: </strong>Despite a low number of observed, potentially associated ADEs, CDSS for DDI management aids physicians to optimize DOAC treatment as the described DDIs can cause significant patient harm. Increased ADE monitoring and larger real-world studies are needed to refine CDS tools and further optimize patient safety.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Heart Failure with Preserved Ejection Fraction Through Regulating Macrophage Polarization Mediated by Alpha7nAChR.","authors":"Jun-Yu Huo, Can Hou, Fang Jia, Cong Xue, Xiao-Long Li, Ling Yang, Wan-Ying Jiang, Xiaoying Zhang","doi":"10.1007/s10557-025-07695-0","DOIUrl":"https://doi.org/10.1007/s10557-025-07695-0","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the effects of transcutaneous auricular vagus nerve stimulation (ta-VNS) on heart failure with preserved ejection fraction (HFpEF) and explore the related mechanisms.</p><p><strong>Methods: </strong>Sprague-Dawley rats were fed a high-fat diet and N^[w]-nitro-L-arginine methyl ester to establish an HFpEF model. Ta-VNS was achieved by electrical stimulation of the auricular concha. Histology and echocardiography were used to identify changes in cardiac function and pathology. RNA sequencing was used to explore the underlying mechanism. RT‒PCR, WB, and immunofluorescence staining were used to determine the effects of ta-VNS on macrophage polarization. In vitro, RAW264.7 cells were induced into the M1 or M2 type. An α7nAChR agonist and an α7nAChR inhibitor were used to explore the effects of α7nAChR on macrophage polarization. Finally, an α7nAChR inhibitor was used to determine whether the therapeutic effects of ta-VNS are related to α7nAChR.</p><p><strong>Results: </strong>In vivo, ta-VNS alleviated cardiac dysfunction and pathological remodeling in rats with HFpEF. RNA sequencing demonstrated that the protective effects of ta-VNS on HFpEF were related to macrophage-mediated inflammatory responses. Ta-VNS decreased the expression of M1-type macrophage markers but increased the expression of M2-type markers. In vitro studies revealed that the α7nAChR agonist decreased the polarization of macrophages toward the M1 type, whereas the α7nAChR inhibitor reduced the polarization toward the M2 type. Furthermore, the α7nAChR inhibitor abolished the protective effects of ta-VNS on macrophage polarization and myocardial remodeling in rats with HFpEF.</p><p><strong>Conclusion: </strong>Ta-VNS ameliorated HFpEF-induced cardiac remodeling, which was associated with the modulation of macrophage polarization.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}