Journal of Cardiovascular Pharmacology最新文献

Abstract: Berberine, the primary active compound in Coptis chinensis Franch, is well known for its anti-infective, hypoglycemic, lipid-lowering, antitumor, and anti-inflammatory effects. This review summarizes the physicochemical and pharmacokinetic characteristics of berberine, its intraintestinal pharmacology involving gut microbiota cross-talk to heart failure (gut-cardiac axis), extraintestinal pharmacology in heart failure, and network pharmacology. Berberine enhances the intestinal barrier, reducing endotoxin entry into the bloodstream. It also regulates the intestinal flora composition, notably altering the Bacillota/Bacteroidota ratio. Importantly, berberine promotes beneficial bacteria while inhibiting pathogenic bacteria. In addition, it influences gut microbiota metabolites, decreasing trimethylamine and trimethylamine N-oxide while increasing short-chain fatty acids. Berberine addresses extraintestinal direct mechanisms by mitigating heart failure risk factors such as atherosclerosis, hyperglycemia, and hyperlipidemia. It also decreases cardiac oxygen consumption, oxidative stress, and endoplasmic reticulum stress, thereby reducing chronic cardiac inflammation, apoptosis, and remodeling, while enhancing myocardial energy to improve cardiac function. Network pharmacology analysis has identified the top 10 hub genes for berberine in heart failure therapy: STAT3, TNF, MTOR, NFKB1, HIF1A, ESR1, BCL2, PTGS2, PPARG, and MMP9. Notably, TNF, HIF1A, and PPARG are key targets for berberine in heart failure with preserved ejection fraction treatment. Berberine shows promise for heart failure treatment, but its bioavailability needs improvement. In addition, the efficacy and safety of berberine in clinical heart failure management, especially in heart failure with preserved ejection fraction, require further evaluation through large-scale, multicenter clinical trials.

Abstract: Testosterone and dihydrotestosterone (DHT) attenuate drug-induced lengthening of ventricular repolarization, but it is unknown whether they influence drug-induced torsades de pointes (TdP). We tested the hypothesis that DHT reduces the incidence and severity of drug-induced TdP. Male New Zealand white rabbits underwent orchiectomy and were implanted with 2 subcutaneous sustained-release pellets containing DHT 50 mg (100 mg, n = 23) or placebo (n = 20). After 7 days, hearts were excised, mounted, and perfused with modified Krebs-Henseleit solution. The atrioventricular node was destroyed manually. Dofetilide 100 nM was perfused for 30 minutes. Median (Q 1 , Q 3 ) serum DHT concentrations were higher in DHT-treated rabbits [314.0 (232.5, 388.6) vs. 32.5 (28.5, 36.2) ng/dL, P < 0.0001]. The incidence of TdP in the DHT and placebo groups was 6/23 (26%) versus 8/20 (40%), respectively ( P = 0.33). In hearts that developed TdP, the median (Q 1 , Q3) number of episodes was lower in the DHT group [2 (2, 3.5) vs. 18.5 (12.5, 20.5), P = 0.01]. The median time to first TdP episode was longer [18.5 (17.3, 21.3) vs. 10.5 (12.5, 20.5) minutes, P = 0.01], and the TdP burden (median total number of TdP beats per heart) was lower in the DHT group [11.5 (9.5-46.5) vs. 271 (99.3-440.3) beats, P = 0.007]. Pre-dofetilide Fridericia-corrected QT intervals were shorter in the DHT group [377 (366, 390) vs. 385 (378, 401) ms, P = 0.02]. Maximum Fridericia-corrected QT interval during dofetilide perfusion was shorter in the DHT group [399 (390, 410) vs. 414 (399, 442) ms, P = 0.007]. In conclusion, DHT diminishes the severity of dofetilide-induced TdP.

Abstract: Arterial hypertension affects >1.28 billion adults globally, remaining a leading cause of cardiovascular morbidity and mortality. Despite effective therapies, suboptimal blood pressure control persists, highlighting the need for precision approaches. Epigenetic biomarkers, particularly DNA methylation (DNAm), have emerged as potential tools to enhance risk stratification and personalize antihypertensive therapy, yet their clinical relevance remains uncertain. To systematically synthesize evidence on genetic and epigenetic biomarkers associated with hypertension, focusing on DNAm signatures, regulatory pathways, and translational potential, we conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, registered in PROSPERO (Chronic Renal Disease (CRD) 420251059256). PubMed, MEDLINE, Embase, and ScienceDirect were searched up to March 2025. Eligible studies investigated genetic or epigenetic markers, such as DNAm, single nucleotide polymorphisms, or chromatin modifications in adult hypertension populations. Data on study design, populations, biomarkers, analytical methods, and outcomes were extracted. Risk of bias was assessed using RoB 2 and Risk of Bias in Nonrandomized Studies of Interventions tool. Twelve studies were included, encompassing cross-sectional and longitudinal designs. DNAm signatures at loci including AGTR1, PHGDH, SLC7A11, Angiotensin-Converting Enzyme (ACE), and WNT3A were recurrently associated with blood pressure regulation. Transancestry genome-wide analyses identified methylation-enriched loci such as KCNK3, PDE3A, and PRDM6. However, no study demonstrated predictive value for clinical end points or robust replication across diverse populations. Methodological heterogeneity limited longitudinal data and underrepresentation of low- and middle-income countries were key limitations. Although epigenetic markers show promise for hypertension research, current evidence remains exploratory. Rigorous, longitudinal studies integrating clinical end points are essential for advancing toward clinical translation.

Abstract: Artificial intelligence (AI) has been increasingly integrated into medical publishing, hopefully improving efficiency and accuracy, but serious concerns persist regarding ethical implications, authorship attribution, and content reliability. We aimed at understanding the perspectives of editors of medical journals on AI. A structured online questionnaire was developed and distributed to editors-in-chief of medical journals worldwide. The survey comprised 27 concise questions exploring demographics, journal practices, and perspectives on AI in editorial workflows. Quantitative data were analyzed using descriptive statistics to summarize usage patterns, perceived benefits, risks, and future expectations. A total of 59 editors-in-chief completed the survey (response rate: 19%), with replies suggesting substantial variability in beliefs and attitudes toward AI for publication in medical journals. Artificial intelligence tools were already in use by 49% of journals, mainly for plagiarism detection (76%) and data verification (35%). Only 9% of responders reported that journals used AI for both scientific and linguistic review. Time savings (79%) and cost reduction (43%) were the most commonly cited benefits, and concerns included potential bias (71%) and lack of accountability (60%). Overall, 81% of responders anticipated a major role for AI in publishing within 10 years. Exploratory analyses suggested several potential associations between replies and respondent or journal features, requiring further validation in future surveys. In conclusion, this survey on attitudes toward AI in publication in medical journals suggests that editors-in-chief are cautiously adopting AI in their editorial workflow, supporting its operational use while explicitly calling for clear guidance to address ethical and regulatory concerns.

Abstract: Pulmonary arterial hypertension (PAH) is a severe disease characterized by significant pulmonary vascular remodeling and right ventricular dysfunction. Activated fibroblasts can induce collagen deposition around blood vessels, thereby promoting vascular hardening and PAH development. Fibroblast activation protein (FAP) is a proline-specific serine protease expressed in active fibroblasts that is closely associated with tissue remodeling, inflammation, fibrosis, tumor growth, and cellular proliferation. However, whether FAP is linked to PAH has not yet been addressed. This study aimed to investigate the potential role of FAP in PAH pathogenesis. In animal models of PAH, we found that FAP expression levels were higher both in vivo and in vitro than in the control group. And FAP inhibitors alleviated pulmonary vascular remodeling and right ventricular function in vivo PAH model. To explain the elevated expression of FAP in PAH, we screened the transcription factor Egr1 of FAP through the databases GTRD and Human TFDB, and demonstrated that the transcriptional activity of early growth response 1 (Egr1) binds to the FAP promoter region and regulates FAP by chromatin immunoprecipitation assay and the dual-luciferase reporter gene assay. Subsequently, we demonstrated that FAP promotes the activation of pulmonary arterial adventitial fibroblasts by enhancing their proliferation, migration, and transformation into muscle fibroblasts. Furthermore, FAP mechanistically affects the PTEN/PI3K/Akt signaling pathway, which is a classic signaling pathway that regulates fibroblast proliferation, migration, and invasion. In summary, FAP plays a crucial role in activating pulmonary arterial adventitial fibroblasts and may be a potential therapeutic target for patients with PAH.

Abstract: Malignant pericardial effusion (MPE) is a progressive fluid accumulation in the pericardial space that can lead to pericardial tamponade. Despite the high recurrence rate associated with pericardiocentesis, it remains the mainstay therapy. Bleomycin has emerged as an intrapericardial sclerosing therapy that may reduce recurrence and improve patients' quality of life. This systematic review aimed to assess the efficacy and safety profile of bleomycin instillation in patients with MPE. An exhaustive search was conducted in PubMed, Web of Science, Scopus, ProQuest, EBSCO, and ClinicalTrials.gov databases. Eligible studies included MPE patients as participants who were treated with intrapericardial bleomycin, reporting the patients' outcomes and using English in the full text. Individual studies were assessed for quality using the Newcastle-Ottawa Scales for cohort studies and the Jadad Scale for trial studies. Eight studies were included in this systematic review involving 242 MPE patients treated with bleomycin. Bleomycin demonstrated lower recurrence rates than other sclerosing agents, with only ≤5% of patients requiring repeated drainage because of recurrence. Bleomycin treatment resulted in 3.5 days less hospitalization compared with doxycycline. Bleomycin is also safe to use, with reported less severe pain compared with other treatment agents for MPE, such as doxycycline and pericardiocentesis. Bleomycin may benefit patients by reducing recurrence rates and improving patients' quality of life. Moreover, it is safe and has low rates of adverse events after the instillation.

Abstract: The extensive use of severe acute respiratory syndrome coronavirus 2 vaccines has played a crucial role in controlling the coronavirus disease 2019 pandemic, underscoring the remarkable advantages and efficacy of novel vaccine technologies. However, rare but life-threatening cardiovascular complications such as myocarditis, pericarditis, and thrombosis have emerged, predominantly affecting young males after their second vaccine dose. These adverse events highlight the importance of continued pharmacovigilance and transparent communication about potential risks. Because the global epidemiologic context has shifted, now characterized by widespread natural, vaccine-induced, or hybrid immunity, it is important to re-evaluate the risk-benefit ratio of repeated vaccine administration in low-risk individuals. Data regarding severe acute respiratory syndrome coronavirus 2 vaccines complications are still largely based on the early phases of the pandemic (2020-2021), when population-level immunity was minimal and severe coronavirus disease 2019 outcomes more frequent. Today, such comparisons may no longer be appropriate. Updated real-world evidence is needed to better inform decision making and ensure that public health strategies remain aligned with the contemporary risk landscape.

Abstract: Recently, apigenin has been widely studied for its antiatherosclerosis properties, but its mechanism remains to be further elucidated. This study aims to evaluate the expression of LOX-1, Bcl-2, and Bax in apigenin-treated atherosclerotic rats and to explore whether apigenin affect the expression of apoptotic genes. We analyzed the relationship between these 3 genes and atherosclerosis based on bioinformatics methods and conducted animal experiments on them. We used a fully automatic analyzer to analyze blood lipid levels and found that apigenin had a good effect on lowering blood lipids. Western blot was used to detect LOX-1 protein, and RT-qPCR was used to detect Bcl-2 and Bax mRNA.The fruit showed that apigenin treatment reduced LOX-1 gene expression while increasing the Bcl-2/Bax ratio. These studies provide an experimental basis for the development of apigenin as a new drug for the treatment of atherosclerosis.