Cardiovascular Therapeutics最新文献

Purpose: This systematic review and meta-analysis of randomized controlled trials (RCTs) is aimed at assessing the clinical efficacy and safety of stellate ganglion block (SGB) for angina pectoris (AP).

Methods: PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang databases were comprehensively searched for RCTs investigating SGB treatment for AP. The retrieval time was from the establishment date of each database to October 10, 2024. The Cochrane risk of bias assessment tool was used to determine the methodological quality. Review Manager 5.4 software was employed for data analysis, and GRADEpro GDT software was utilized to evaluate the quality of evidence.

Results: Ultimately, six RCTs were included, encompassing 373 patients with angina. The overall methodological quality of the included studies was moderate, with the evaluation of evidence quality showing 12 low-quality and five extremely low-quality studies. The meta-analysis results demonstrated that compared with the control group, the experimental group had lower frequency and duration of AP, visual analog scale score, heart rate, detection rate of S-T segment elevation ≥ 0.1 mV on electrocardiogram (ECG) after 24 h of treatment, detection rate of abnormal T waves on ECG after 24 h of treatment, and S-T segment displacement on ECG after treatment. Furthermore, the experimental group exhibited lower serum Cardiac Troponin I levels, a decreased incidence of acute myocardial infarction (AMI) and rehospitalization, and improved clinical efficacy. However, none of the included studies reported SGB-related adverse events.

Conclusion: SGB is effective in alleviating myocardial injury and reducing the incidence of AMI and rehospitalization in patients with AP. Nevertheless, the limited number and relatively low quality of included studies emphasize the requirement for more high-quality research to verify these conclusions.

Purpose: Myocardial infarction (MI), a severe cardiovascular disease, is the result of insufficient blood supply to the myocardium. Despite the improvements of conventional therapies, new approaches are needed to improve the outcome post-MI. Imperatorin is a natural compound with multiple pharmacological properties and potential cardioprotective effects. Therefore, this work investigated imperatorin’s therapeutic effects and its mechanism of action in an MI mouse model.

Methods: Network pharmacology, molecular docking, and experimental validation were performed for exploring the pharmacokinetic properties, therapeutic effects, and molecular targets of imperatorin in MI. Permanent ligation of the left anterior descending artery was performed in male C57BL/6 mice to induce MI before treatment with imperatorin once per day for 1 week. Echocardiography, heart histology, RNA sequencing, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) as well as western blotting were carried out for evaluating cardiac function and structure, as well as gene and protein expression.

Results: Imperatorin significantly improved cardiac function, preserved cardiac structure, attenuated cardiac remodeling and fibrosis, and reduced cardiomyocyte apoptosis in MI mice. Eight differentially expressed genes overlapping with key target genes were found, two upregulated and six downregulated. A key target in signaling pathways associated with imperatorin effect in MI was angiotensin-converting enzyme (ACE). Imperatorin inhibited ACE–angiotensin II (Ang II)–angiotensin II Type 1 receptor (AT1R) axis in MI mice.

Conclusion: Imperatorin attenuated MI by inhibiting the ACE–Ang II–AT1R axis. Thus, imperatorin might be considered a potential therapeutic agent to cure MI.

Coronary artery disease (CAD) is the leading cause of death worldwide in both men and women. Accordingly, we retrospectively reviewed the effects of various risk factors on coronary angiographic outcomes. Data were collected from the catheter lab through Tripoli University Hospital records, whereas the team reviewed clinical data and coronary artery diagrams for 1 year from 01/04/2019 to 31/03/2020. In our study, the total number of cases was 666, 401 male and 265 female, aged between 27 and 91 years. Our analysis revealed a significantly higher incidence of CAD among male smokers under 60. Conversely, a majority of nonsmoker patients were female. The most common risk factors for women were diabetes mellitus (DM) and hypertension (HTN) (12% and 13%, respectively). While the men share the significant effects of smoking on coronary angiography (C. Angio) findings (40.52%), most of them underwent a percutaneous coronary intervention (PCI). In our study, there was evidence that CAD is a prevalent disease among middle-aged populations with male gender preference. The risk factors, including diabetes, HTN, and smoking, are the most contributing factors for developing CAD in Libya.

Background: Dose adjustments of direct-acting oral anticoagulants (DOACs) for atrial fibrillation are based on pivotal clinical trials assessing their effectiveness and safety in controlled settings. However, the appropriateness of these dosing strategies in real-world practice is uncertain. The purpose of this study is to compare the effectiveness and safety of dose-specific DOACs with those of warfarin.

Methods: This study retrieved articles from MEDLINE, Embase, and CENTRAL until March 5, 2024. Primary outcomes were the incidence of stroke/systemic embolisms (S/SEs) and major bleeding (MB). Direct pairwise meta-analyses compared each dose-specific DOAC with warfarin. Heterogeneity was assessed using Higgin’s I² and Q statistics, while publication bias was evaluated through funnel plots and Begg’s and Egger’s tests, with adjusted pooled estimates calculated via trim-and-fill and precision-effect estimate with standard error (PET-PEESE) methods. A network analysis was conducted, with additional comparisons made using a Bayesian random-effects model for indirect evidence.

Results: A total of 32 studies with 2,332,770 patients were included. Both standard-dose (SD) and low-dose (LD) DOACs significantly reduced S/SE, except for LD apixaban and LD edoxaban. Rivaroxaban did not show significant difference in MB compared to warfarin. In East Asian patients, all doses of DOACs exhibited lower hazard ratios (HRs) for S/SE and MB than those observed in the primary analysis, with LD rivaroxaban significantly reducing MB, a finding not observed in the primary analysis. Rank probability analysis indicated that the dose-specific DOACs had different safety profiles and small but meaningful differences in effectiveness. SD apixaban (S/SE: second, MB: second) and edoxaban (S/SE: first, MB: fourth) and LD edoxaban (S/SE: fourth, MB: first) had high ranks. LD apixaban had the most significant difference in rank for S/SE from SD apixaban, ranking eighth compared to second.

Conclusions: This study found that all DOACs provided comparable or superior effectiveness and safety to warfarin. SD apixaban, SD edoxaban, and LD edoxaban achieved a favorable balance between preventing S/SE and MB risk.

Acute coronary syndrome (ACS) is one of the most common leading global causes of mortality, encompassing ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA). Percutaneous coronary intervention (PCI) has become a pivotal therapeutic approach for ACS, underscoring the importance of anticoagulation strategies. Among the commonly employed anticoagulants in PCI, heparin and bivalirudin take precedence, with heparin serving as the archetypal choice. Nevertheless, the determination of an optimal anticoagulation regimen remains a point of contention in contemporary clinical practice. To address the differences in anticoagulants during PCI, we meticulously conducted a literature review through PubMed and Web of Science, employing search terms such as “heparin,” “bivalirudin,” “percutaneous coronary intervention,” and “acute coronary syndrome.” For patients with PIC brought on by STEMI, NSTEMI, and stable or UA pectoris, the review focused on randomized controlled trials to assess and compare the efficacy and safety of heparin and bivalirudin as anticoagulant options. This systematic review is aimed at furnishing valuable insights into the ongoing debate surrounding the choice of anticoagulation regimens in PCI. By scrutinizing clinical evidence derived from relevant trials, we seek to inform and guide healthcare practitioners in making informed decisions based on the unique requirements of patients with various ACS presentations.

Background: Thymidine phosphorylase (TYMP) promotes platelet activation and thrombosis while suppressing vascular smooth muscle cell (VSMC) proliferation. Both processes are central to the development and progression of abdominal aortic aneurysms (AAAs). We hypothesize that TYMP plays a role in AAA development.

Methods: Male wild-type (WT) C57BL/6J and Tymp^−/− mice, fed a Western diet (WD) (TD.88137), were subjected to the 4-week Ang II infusion–induced AAA model. AAA progression was monitored by echography and confirmed through necropsy. Whole-body inflammation was assessed using a plasma cytokine array. Mechanistic studies were conducted using TYMP-overexpressing rat VSMC cell lines and primary VSMCs cultured from WT and Tymp^−/− mouse thoracic aortas. Histological studies were performed on human AAA and normal aorta samples.

Results: Elevated TYMP levels were observed in human AAA vessel walls. While WT mice exhibited a 28.6% prevalence of Ang II infusion–induced AAA formation, Tymp^−/− mice were protected. TYMP enhanced MMP2 expression, secretion, and activation in VSMCs, which was inhibited by tipiracil, a selective TYMP inhibitor. Systemically, TYMP promoted proinflammatory cytokine expression, and its absence attenuated TNF-α-induced MMP2 and AKT activation. WT VSMCs treated with platelets lacking TYMP showed a higher proliferation rate than cells treated with WT platelets. Additionally, TYMP increased activated TGFβ1 expression in cultured VSMCs and human AAA vessel walls. In WT VSMCs, TYMP augmented thrombospondin-1 type 1 repeat domain (TSR)–stimulated TGFβ1 signaling, increasing connective tissue growth factor and MMP2 production. TSR also enhanced AKT activation in WT VSMCs but had the opposite effect in Tymp^−/− cells. TSR-enhanced MMP2 activation in WT VSMCs was attenuated by LY294002 (a PI3K inhibitor) but not by SB431542 (a TGFβ1 inhibitor); both inhibitors had indiscernible effects on Tymp^−/− VSMC.

Conclusion: TYMP emerges as a novel regulatory force in vascular biology, influencing VSMC function and inflammatory responses to promote AAA development.

The left ventricular pressure–strain loop (PSL) is a new technique based on ultrasound for noninvasive quantitative evaluation of global and local myocardial work (MW). This study is aimed at evaluating improvement factors of patients with heart failure (HF) reduced ejection fraction (HFrEF) using the PSL technique. A total of 88 patients with HF were enrolled in this study, which had ≤ 40% left ventricular ejection fraction (LVEF). The EchoPAC workstation was used to obtain the global longitudinal strain (GLS) and MW parameters of the left ventricle. All patients have taken medicines for HF treatments for 6–12 months. The improvements of HF after therapies were evaluated according to the following recommended criteria. The clinical characteristics of patients with improved and nonimproved groups were stratified via univariate or multivariate logistic regression analysis, receiver operating characteristic (ROC), and the area under ROC (area under the curve (AUC)). There were no significant differences in general medical information, the underlying diseases, laboratory findings, myocardial enzyme activities, and taking medicines between the improved and nonimproved LVEF patients (p > 0.05). There were significant differences in LVEF of patients at admission, left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness (IVST), early diastolic mitral flow peak velocity E (E peak), GLS, global myocardial work index (GWI), global myocardial constructive work (GCW), and global myocardial work efficiency (GWE) between the two groups (p < 0.05). Univariate and multivariate logistic regression analyses confirmed that GWI and GCW were critical predictive factors for LVEF improvement in patients with HF. ROC curve showed that the AUC of GWI and GCW were 0.796 and 0.779 at the cut-off of 741 mmHg% for GWI and 973.5 mmHg% for GCW, respectively. The sensitivities of GWI and GCW were 65% and 75%, and the specificities of GWI and GCW were 83.3% and 79.2% at given cut-off values. These results revealed that GWI and GCW were independent predictors of improvement of LVEF in patients with HFrEF.

Ischemic heart disease (IHD) remains one of the most prominent causes of mortality and morbidity globally, and the risk of ischemia–reperfusion injury is becoming more severe and constant. This underscores the need to develop new methods to protect the heart from damage. DJ-1 is a multifunctional intracellular protein encoded by the PARK7 gene that plays roles in processes including the control of autophagy, the preservation of mitochondrial integrity, the prevention of apoptosis, and the elimination of oxidative stress. DJ-1 has recently been the focus of growing interest as a target molecule relevant to treating myocardial ischemia–reperfusion injury due to its protective properties and its role in cellular response mechanisms. Consistently, DJ-1-related interventions, such as its exogenous administration or the use of pharmacological agents, have been demonstrated to help protect the myocardium from ischemia–reperfusion injury and associated adverse outcomes. This review provides an overview of DJ-1 and its therapeutic relevance in the myocardium in the setting of ischemia and reperfusion.

Background: Doxorubicin (DOX) is a widely used antitumor drug; however, its use is limited by the risk of serious cardiotoxicity. Dehydroevodiamine (DHE) is a quinazoline alkaloid which has antiarrhythmic effects. The aim of this study was to investigate the protective effect of DHE on doxorubicin-induced cardiotoxicity (DIC) and its potential mechanism.

Materials and Methods: Rat H9c2 cardiomyocytes were exposed to DOX for 24 h to establish a DOX-induced cardiomyocyte injury model. DHE and ErbB inhibitor AG1478 were used to treat H9c2 cells to investigate their effects. Cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays were used to evaluate cell viability. Flow cytometry and caspase-3 activity assay were used to detect apoptosis. Western blot was used to detect the expression levels of apoptosis-related proteins and neuregulin-1 (NRG1)/ErbB pathway–related proteins. The levels of proinflammatory cytokines and markers of oxidative stress were also detected, respectively. Quantitative polymerase chain reaction (qPCR) was used to detect mRNA expression levels of hub genes.

Results: DHE enhanced cardiomyocyte viability and decreased LDH release in a concentration- and time-dependent manner. DHE also significantly inhibited DOX-induced cardiomyocyte apoptosis, inflammation, and oxidative stress. Bioinformatics analysis showed that the protective mechanism of DHE against DIC was related to ErbB signaling pathway. DOX treatment significantly reduced NRG1, p-ErbB2, and p-ErbB4 protein expression levels in cardiomyocytes, while DHE pretreatment reversed this effect. ErbB inhibitor AG1478 reversed the protective effect of DHE on cardiomyocytes.

Conclusion: DHE protects cardiomyocytes against DOX by regulating NRG1/ErbB pathway. DHE may be a potential agent for the prevention and treatment of DIC.

Background: Cysteinyl leukotrienes (LTs) and their receptors are involved in the pathogenesis of abdominal aortic aneurysms (AAAs). However, whether CysLT1 receptor antagonists such as montelukast can influence experimental nondissecting AAA remains unclear.

Methods: Nondissecting AAAs were induced in C57BL/6J mice by transient aortic luminal infusion of porcine pancreatic elastase (PPE). All animals were administrated montelukast (1 or 10 mg/kg, daily) or vehicle by gavage beginning 1 day before PPE infusion for 14 days. On day 0 (baseline) and day 14 after PPE infusion, abdominal aortic diameters were directly measured. Aortic aneurysmal segment samples were collected, and histopathological analysis was performed.

Results: Compared to vehicle treatment, montelukast significantly decreased PPE infusion–induced aortic expansion in a dose-dependent manner (0.09-mm reduction at a low dose and 0.19-mm reduction at a high dose). Histopathological analysis also revealed that compared with vehicle treatment, montelukast treatment, especially in the high-dose group, significantly improved PPE-induced aortic elastin degradation and medial smooth muscle cell depletion. Both doses of montelukast also markedly decreased the number of local leucocytes, including macrophages, CD4⁺ T cells, CD8⁺ T cells, and B cells, infiltration and accumulation in aortic aneurysmal lesions. Montelukast treatment also downregulated matrix metalloproteinase 2 (MMP2) and MMP9 expression and inhibited mural angiogenesis in aneurysmal aortas.

Conclusion: Montelukast treatment improves experimental nondissected AAAs in mice partly by improving aortic inflammation.