Cardiovascular Drugs and Therapy最新文献

Abdominal aortic aneurysm (AAA) is a chronic aortic disease that currently lacks effective pharmacological treatments. Growth Differentiation Factor 11 (GDF11) is a member of transforming growth factor β (TGF-β) superfamily associated with cardiovascular diseases. Transcriptomic analysis of GSE57691 revealed significantly reduced GDF11 expression in AAA tissues, with further decline from early- to advanced-stage disease. GDF11 levels correlated negatively with IL-1β, IL-6, MMP-2, and MMP-9, and positively with ACTA2 and TGF-β/Smad2/3 signaling. In an Ang II-induced AAA model of ApoE^-/- mice, GDF11 was markedly decreased, accompanied by inflammation, matrix degradation, and vascular remodeling. AAV-mediated GDF11 overexpression improved survival, reduced AAA incidence, limited aortic dilation, and attenuated elastin degradation and collagen deposition. Mechanistically, GDF11 inhibited inflammatory cytokines, downregulated MMP-2/9, restored ACTA2, and modulated TGF-β/Smad2/3 signaling. In vitro, GDF11 attenuated Ang II-induced phenotypic switching of vascular smooth muscle cells (VSMCs), while inhibition of TGF-β/Smad2/3 signaling reversed these effects. In conclusion, GDF11 mitigates AAA progression by suppressing inflammation, preserving extracellular matrix integrity, and maintaining VSMC phenotype via TGF-β/Smad2/3 signaling, highlighting its potential as a therapeutic target for AAA.

Background: Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, constitutes a significant cause of postoperative morbidity and mortality among surgical patients. Despite the widespread use of low-molecular-weight heparin (LMWH) for thromboprophylaxis, conventional fixed-dose regimens frequently yield subprophylactic anti-factor Xa (anti-Xa) levels, particularly in individuals with obesity, renal impairment, or altered drug pharmacokinetics. These interindividual variations in LMWH pharmacodynamics underscore the need for personalized anticoagulant strategies. Anti-Xa-guided dosing has emerged as a strategy to individualize prophylaxis and optimize outcomes.

Objective: To summarize evidence on individualized LMWH thromboprophylaxis, focusing on anti-Xa-guided strategies, their clinical efficacy, and limitations in real-world implementation.

Methods: A systematic literature review was conducted to identify studies evaluating fixed-dose, weight-based, and anti-Xa-adjusted LMWH prophylaxis across trauma, surgical, intensive care, and oncology settings.

Results: Across multiple studies, up to 87.7% of patients receiving fixed-dose LMWH were found to have subtherapeutic anti-Xa levels, particularly in surgical and obese cohorts. Dose adjustment based on anti-Xa monitoring was consistently associated with improved attainment of prophylactic levels and lower VTE incidence, without a significant increase in major bleeding events. However, heterogeneity in study design, small sample sizes, and the lack of large randomized trials limit broad clinical adoption.

Conclusions: Evidence supports the potential benefit of individualized LMWH dosing guided by anti-Xa monitoring in selected patient populations. Standardization of testing protocols and prospective validation are needed to enable widespread clinical application.

Purpose: Anemia is common among women undergoing elective percutaneous coronary intervention (PCI), yet remains under-addressed in contemporary ACC/AHA guidelines. We evaluated the association between baseline anemia and short- and long-term outcomes after PCI.

Methods: Using the TriNetX federated electronic health record network, we identified women undergoing first-time elective PCI and compared anemic vs. non-anemic patients. One-to-one propensity score matching yielded N = 1,153 per group, balancing demographics, comorbidities, medications, and labs. Clinical outcomes were assessed at 7 days, 30 days, 6 months, and 12 months, and included major adverse cardiovascular events (MACE), acute coronary syndrome (ACS), acute kidney injury (AKI), stroke or transient ischemic attack (TIA), major bleeding, transfusion requirements, all-cause hospitalization, in-stent restenosis, stent thrombosis, and all-cause mortality. Hazard ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards models.

Results: At 7 days post-procedure, baseline anemia was significantly associated with an increased risk of AKI (HR 2.2; 95% confidence interval [CI], 1.1-4.5; p = 0.03), major bleeding events (HR 3.2; 95% CI, 1.4-7.5; p < 0.01), and transfusion requirements (HR 9.1; 95% CI, 2.1-39.2; p < 0.01). Notably, all 7-day mortality events occurred in the anemic cohort (0.9% vs. 0.0%). By 30 days, patients with anemia continued to demonstrate higher rates of AKI, major bleeding, and transfusion needs. At 12 months, these risks persisted and, in some cases, widened. Anemia was independently associated with increased rates of major adverse cardiovascular events (MACE) (HR 1.4; 95% CI, 1.1-1.8; p = 0.01), AKI (HR 1.9; 95% CI, 1.5-2.5; p < 0.01), all-cause hospitalization (HR 1.3; 95% CI, 1.1-1.5; p < 0.01), and all-cause mortality (HR 2.3; 95% CI, 1.4-3.8; p < 0.01). Differences in stroke or TIA rates were not statistically significant, and the incidence of stent thrombosis or restenosis was comparable between anemic and non-anemic groups.

Conclusions: Among women undergoing elective PCI, baseline anemia emerged as a strong predictor of adverse outcomes, spanning early kidney/bleeding complications and sustained increases in MACE, hospitalizations, and mortality over one year, without clear differences in stent-related events. These data support integrating anemia into pre-PCI risk assessment and motivate randomized trials of pre-procedural anemia optimization.

Purpose: While reperfusion is essential for restoring blood flow, it can paradoxically exacerbate myocardial injury by disrupting energy metabolism, leading to cell necrosis, apoptosis, and structural damage. Despite the significance of ischemia-reperfusion (I/R) injury, effective treatments remain scarce, highlighting the need for a deeper understanding of its underlying mechanisms to develop targeted therapies.

Methods: A rat model of myocardial I/R injury and a H9c2 cell-based hypoxia/reoxygenation (H/R) model were utilized for primary validation. HOXB5 was overexpressed several days prior to I/R or H/R induction. Gene and protein expression were assessed by RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry. Mitochondrial function and ferroptosis were analyzed by commercial kits. The regulatory relationship among Lin28a, HOXB5, and Sirt5 was examined using RIP, ChIP-PCR, and dual-luciferase assays.

Results: HOXB5 expression was significantly reduced in infarcted myocardial tissue following I/R injury, of which overexpression attenuated H/R-trigged apoptosis to motivate H9c2 cell survival. Meanwhile, HOXB5 overexpression decreased mitochondrial ROS production, improved mitochondrial respiration, mitochondrial complexes (I, II, III, and V) activity, and reduced mitophagy under H/R conditions in H9c2 cells. Mechanistically, Lin28A was identified as a regulator of HOXB5, which in turn transcriptionally activated Sirt5. Furthermore, the protective effects of HOXB5 overexpression on myocardial histological damage and cardiac function through modulating ferroptosis in rats' I/R injury was abrogated by Sirt5 knockdown.

Conclusion: Our study reveals the crucial role of HOXB5 in maintaining mitochondrial homeostasis and regulating mitophagy, which in turn protects cardiomyocytes from I/R injury through Sirt5. These findings underscore the HOXB5-Sirt5 pathway as a promising therapeutic target for mitigating I/R injury.

The study by Kimoto et al. investigated the relationship between metabolic syndrome (MetS) and breast cancer incidence in a large Japanese cohort exceeding one million women, revealing an unexpected age-dependent pattern. Both pre-MetS and MetS were associated with a lower incidence of breast cancer, particularly in women younger than 50 years, whereas this association attenuated or reversed after 60 years of age. In our correspondence, we discuss potential biological and methodological explanations for this paradox. We highlight the importance of heterogeneity in MetS definitions (Japanese vs. modified ATP III), the role of menopausal status beyond chronological age, and possible confounding by screening behavior and competing cardiovascular mortality. While the authors' interpretation involving anovulatory cycles and adipose-derived estrogen provides a plausible mechanistic framework, we emphasize the need for analyses stratified by actual menopausal status, repeated measures of MetS components, and competing-risk modeling. Overall, the findings underscore the complex, age-modulated interaction between metabolic dysregulation and breast carcinogenesis, reinforcing the necessity of menopause-specific risk assessment and standardized MetS definitions in future research.