Cardiovascular Drugs and Therapy最新文献

{"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":"https://doi.org/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}

{"title":"Is Bivalirudin Efficacious in STEMI Patients Undergoing Primary PCI?","authors":"Jayesh Valecha, Sunil Konipineni, Diptish Wankhade, Rahul Kumbhojkar, Divya Shivakumar, Amanda Cyntia Lima Fonseca Rodrigues","doi":"10.1007/s10557-025-07692-3","DOIUrl":"https://doi.org/10.1007/s10557-025-07692-3","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771433","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":"Letter to the Editor Regarding the SELECT Trial.","authors":"Michail Penteris, Konstantinos Lampropoulos","doi":"10.1007/s10557-025-07686-1","DOIUrl":"https://doi.org/10.1007/s10557-025-07686-1","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762998","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":"MOTS-c: Magical Molecule for Diabetic Cardiomyopathy?","authors":"Veera Ganesh Yerra, Kim A Connelly","doi":"10.1007/s10557-025-07689-y","DOIUrl":"https://doi.org/10.1007/s10557-025-07689-y","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763000","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":"Transcatheter Tricuspid Valve Replacement Versus Totally Thoracoscopic Beating-Heart Surgery for Tricuspid Regurgitation.","authors":"Yiwei Wang, Yang Liu, Xuezeng, Mengen Zhai, Xin Meng, Ping Jin, Fanglin Lu, Jian Yang","doi":"10.1007/s10557-025-07669-2","DOIUrl":"https://doi.org/10.1007/s10557-025-07669-2","url":null,"abstract":"<p><strong>Purpose: </strong>Totally thoracoscopic and beating-heart techniques used in tricuspid valve surgery (TTC-TVS) show favorable outcomes. Transcatheter tricuspid valve replacement (TTVR) is an increasingly utilized alternative for patients with tricuspid regurgitation (TR) at high surgical risk. The purpose of this study was to compare TTVR with TTC-TVS to examine the outcomes of these two different management protocols for patients with symptomatic severe TR.</p><p><strong>Methods: </strong>A total of 116 patients with symptomatic severe TR were retrospectively collected and divided into the TTVR (n = 38) and the TTC-TVS (n = 78) groups. The primary end points included 2-year all-cause mortality and the combined endpoint (all-cause mortality and hospitalizations for heart failure).</p><p><strong>Results: </strong>At a median follow-up of 630 (IQR 450-720) days, the similar freedom from 2-year all-cause mortality (85.2% vs. 70.8%; log-rank P = 0.13) and different freedom from combined endpoint (75.3% vs. 49.8%; log-rank P = 0.0049) were followed in TTVR and TTC-TVS. After stratification by TRI-SCORE, TTVR subgroups showed significant difference in combined endpoint, and both also showed significant difference compared to the corresponding TTC-TVS subgroups (all log-rank P < 0.05). In multivariate Cox regression analysis, TRI-SCORE ≥ 6 was independently correlated with all-cause mortality (HR 3.913, 95% CI 1.481-10.337; P = 0.006) and combined endpoint (HR 4.070, 95% CI 1.924-8.608; P < 0.001).</p><p><strong>Conclusions: </strong>TTVR may offer greater benefit compared to TTC-TVS for sicker patients with severe TR. However, this observation should be interpreted within a specific clinical context emphasizing the importance of early intervention.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763050","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":"Cardiorenal Syndrome in Right Heart Failure Due to Pulmonary Arterial Hypertension-The Right Ventricle as a Therapeutic Target to Improve Renal Function.","authors":"Kenzo Ichimura, Adam Gross, Roy O Mathew, Loay Salman, Sushma Reddy, Edda Spiekerkoetter, Mandeep S Sidhu","doi":"10.1007/s10557-024-07588-8","DOIUrl":"10.1007/s10557-024-07588-8","url":null,"abstract":"<p><p>Cardiorenal syndrome (CRS) due to right ventricular (RV) failure is a disease entity emerging as a key indicator of morbidity and mortality. The multifactorial aspects of CRS and the left-right ventricular interdependence complicate the link between RV failure and renal function. RV failure has a direct pathophysiological link to renal dysfunction by leading to systemic venous congestion in certain circumstances and low cardiac output in other situations, both leading to impaired renal perfusion. Indeed, renal dysfunction is known to be an independent predictor of mortality in patients with pulmonary arterial hypertension (PAH) and RV failure. Thus, it is important to further understand the interaction between the RV and renal function. RV adaptation is critical to long-term survival in patients with PAH. The RV is also known for its remarkable capacity to recover once the aggravating factor is addressed or mitigated. However, less is known about the renal potential for recovery following the resolution of chronic RV failure. In this review, we provide an overview of the intricate relationship between RV dysfunction and the subsequent development of CRS, with a particular emphasis on PAH. Additionally, we summarize potential RV-targeted therapies and their potential beneficial impact on renal function.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"373-384"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283000","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":"Agathis dammara Extract and its Monomer Araucarone Attenuate Abdominal Aortic Aneurysm in Mice.","authors":"Qingyi Zhang, Zeyu Cai, Zhewei Yu, Chang Di, Yingkun Qiu, Rong Qi","doi":"10.1007/s10557-023-07518-0","DOIUrl":"10.1007/s10557-023-07518-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Abdominal aortic aneurysm (AAA) is a chronic vascular disease wherein the inflammation of vascular smooth muscle cells (VSMCs) plays a pivotal role in its development. Effectively mitigating AAA involves inhibiting VSMC inflammation. Agathis dammara (Lamb.) Rich, recognized for its robust anti-inflammatory and antioxidant attributes, has been employed as a traditional medicinal resource. Nonetheless, there is a dearth of information regarding the potential of Agathis dammara extract (AD) in attenuating AAA, specifically by diminishing vascular inflammation, notably VSMC inflammation. Furthermore, the active constituents of AD necessitate identification.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;This study sought to ascertain the efficacy of AD in reducing AAA, evaluate its impact on VSMC inflammation, and elucidate whether the monomer araucarone (AO) in AD acts as an active component against AAA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;The extraction of AD was conducted and subjected to analysis through High-Performance Liquid Chromatography (HPLC) and mass spectrometry. The isolation of the AO monomer followed, involving the determination of its content and purity. Subsequently, the effects of AD and AO on VSMC inflammation were assessed in vitro, encompassing an examination of inflammatory factors such as IL-6 and IL-18, as well as the activation of matrix metalloproteinase 9 (MMP9) in tumor necrosis factor-alpha (TNF-α)-stimulated VSMCs. To explore the inhibitory effects of AD/AO on AAA, C57BL/6J male mice were subjected to oral gavage (100 mg/kg) or intraperitoneal injection (50 mg/kg) of AD and AO in a porcine pancreatic elastase (PPE)-induced AAA model (14 days). This facilitated the observation of abdominal aorta dilatation, remodeling, elastic fiber disruption, and macrophage infiltration. Additionally, a three-day PPE mouse model was utilized to assess the effects of AD and AO (administered at 100 mg/kg via gavage) on acute inflammation and MMP9 expression in blood vessels. The mechanism by which AD/AO suppresses the inflammatory response was probed through the examination of NF-κB/NLRP3 pathway activation in VSMCs and aortas.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Liquid Chromatography-Mass Spectrometry (LC-MS) revealed that AO constituted 15.36% of AD's content, with a purity of 96%. Subsequent pharmacological investigations of AO were conducted in parallel with AD. Both AD and AO exhibited the ability to inhibit TNF-α-induced VSMC inflammation and MMP production in vitro. Furthermore, both substances effectively prevented PPE-induced AAA in mice, whether administered through gavage or intraperitoneal injection, evidenced by decreased vascular diameter dilation, disruption of elastin fiber layers, and infiltration of inflammatory cells. In the three-day PPE mouse model, AD and AO mitigated the heightened expression of inflammatory factors and the elevated expression of MMP9 induced by PPE. The activation o","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"239-257"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396541","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":"Use of Antihypertensive Drugs and Arterial Stiffness in the Longitudinal Study of Adult Health (ELSA-Brasil).","authors":"Isabella Viana Gomes Schettini, Sandhi Maria Barreto, Luisa Campos Caldeira Brant, Antônio Luiz Pinho Ribeiro, José Geraldo Mill, Danyelle Romana Alves Rios, Roberta Carvalho Figueiredo","doi":"10.1007/s10557-023-07529-x","DOIUrl":"10.1007/s10557-023-07529-x","url":null,"abstract":"<p><strong>Objective: </strong>Evaluate the longitudinal association between BP control and the use of antihypertensive classes with arterial stiffness (AS) in Brazilian adults.</p><p><strong>Methods: </strong>This study included 1830 participants with arterial hypertension (1092 participants with controlled BP and 738 participants with uncontrolled BP) from the Longitudinal Study of Adult Health (ELSA-Brasil). AS was assessed by pulse wave velocity (PWV) and pulse pressure (PP) at baseline and repeated after approximately 9 years. Associations between AS and BP control and the use of antihypertensives, diuretics, angiotensin-converting enzyme inhibitors (ACEI), AT1 receptor blockers (ARB), calcium channel blockers (CCB), and beta blockers (in the population with controlled BP), at baseline were investigated using linear mixed-effects models.</p><p><strong>Results: </strong>Uncontrolled BP was associated with worse PWV and PP trajectory, respectively (β = 0.026 [0.008 to 0.036] / β = 0.273 [0.216 to 0.330]). Among the participants with controlled BP, using CCB (β = 0.031 [0.011 to 0.051]) was associated with a worse PWV trajectory, compared to not using this class and this combination, respectively.</p><p><strong>Conclusion: </strong>BP control, regardless of the class of antihypertensive used is associated with a better AS trajectory, as assessed by PWV and PP. Among participants with controlled BP, the use of BCC, compared to not using this class, seems to be worse for the trajectory of PWV in individuals with arterial hypertension without cardiovascular disease. Further studies are needed to assess whether this effect results in a better prognosis for patients with arterial hypertension.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"287-296"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797888","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}