Cardiovascular Drugs and Therapy最新文献

Implications of epicardial adipose tissue (EAT) on the development of coronary artery disease (CAD) have garnered recent attention. Located between the myocardium and visceral pericardium, EAT possesses unique morphological and physiological contiguity to the heart. The transcriptome and secretome of EAT differ from that of other fat stores in the body. Physiologically, EAT protects the adjacent myocardium through its brown-fat-like thermogenic function and rapid fatty acid oxidation. However, EAT releases pro-inflammatory mediators acting on the myocardium and coronary vessels, thus contributing to the development and progression of cardiovascular diseases (CVD). Furthermore, EAT-derived mesenchymal stromal cells indicate promising regenerative capabilities that offer novel opportunities in cell-based cardiac regeneration. This review aims to provide a comprehensive understanding and unraveling of EAT mechanisms implicated in regulating cardiac function and regeneration under pathological conditions. A holistic understanding of the multifaceted nature of EAT is essential to the future development of pharmacological and therapeutic interventions for the management of CVD.

Purpose: This meta-analysis aimed to conduct a systematic evaluation of the comparative efficacy and safety of new oral anticoagulants (NOACs) versus warfarin for the treatment of deep venous thrombosis (DVT).

Methods: A systematic computerized search of databases including PubMed, Medline, Web of Science, Embase, Cochrane Library, and www.

Clinicaltrials: gov . was performed to gather research on the efficacy and safety of NOACs versus warfarin in the treatment of DVT, encompassing all records from the inception of each database through September 2024. The discrete data were presented as odds ratios (ORs) with their corresponding 95% confidence intervals (CIs), and the meta-analysis was executed utilizing the Review Manager 5.4.1 and Stata 16 softwares.

Results: A comprehensive analysis of 16 studies encompassing 10,084 patients was conducted, with 6704 individuals in the experimental group receiving NOACs and 3380 in the control group treated with warfarin. The findings are as follows: (1) NOACs demonstrated enhanced treatment efficacy over warfarin, particularly in achieving vascular patency (OR = 1.57, 95% CI (1.09, 2.24), P = 0.01). (2) Regarding the incidence of major bleeding events (OR = 0.65, 95% CI (0.54, 0.78), P < 0.00001), other clinical adverse events-including pulmonary embolism, mortality, stroke, myocardial infarction and recurrent thrombosis (OR = 0.77, 95% CI (0.67, 0.88), P = 0.0002), and post-thrombotic syndrome (PTS) (OR = 0.62, 95% CI (0.47, 0.80), P = 0.0003); NOACs offered improved safety profiles in comparison to warfarin. Furthermore, subgroup analysis revealed that the preventive efficacy of NOACs against PTS improves with longer follow-up periods (P = 0.02).

Conclusion: NOACs have demonstrated superior efficacy and safety profiles in the treatment of DVT compared to traditional warfarin anticoagulant therapy.

Clinical trial registration: This project did not involve any clinical data collection; the data utilized were derived from articles published in PubMed.

Purpose: To investigate the protective effect and mechanism of enhanced expression of endogenous macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury.

Methods: A recombinant double-stranded adeno-associated virus serotype 9 with MIF or green fluorescent protein (GFP) genes (dsAAV9-MIF/GFP) was transduced into mice and neonatal rat ventricular myocytes (NRVMs). The models of cardiac 60 min ischemia and 24 h reperfusion and 12 h hypoxia/12 h reoxygenation (H/R) were established in mice and NRVMs, respectively. Infarct size, cardiac remodeling, and related signaling pathways were assessed.

Results: The dsAAV9 vector demonstrated strong transduction efficacy and cardiac affinity. Cardiac overexpression of MIF led to a 35.3% reduction in infarct size and improved cardiac function following I/R injury. In the dsAAV9-MIF group, the AMP-activated protein kinase (AMPK) signaling pathway was activated, and autophagy was enhanced during the ischemic period. During reperfusion, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway was upregulated, leading to reduced cardiac apoptosis. In vitro, transfection with MIF in NRVMs also upregulated AMPK and ERK1/2 signaling during hypoxia and reoxygenation, respectively. Furthermore, MIF overexpression significantly improved autophagy and mitochondrial function, evidenced by an increased LC3-II/I ratio and enhanced mitochondrial membrane potential (ΔΨm), with these effects reversed by the AMPK inhibitor compound C. Additionally, MIF overexpression led to a 60% reduction in the apoptosis rate of cardiomyocytes subjected to H/R and decreased the Bax/Bcl-2 ratio, partially through the ERK1/2 signaling pathway.

Conclusion: Enhanced endogenous MIF expression via the dsAAV9 vector provides significant cardioprotection against I/R injury by activating the AMPK and ERK1/2 signaling pathways. Our findings suggest that targeting MIF may represent a viable therapeutic strategy for severe and prolonged I/R injury.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Purpose: Cancer patients face a four- to sevenfold higher risk of venous thromboembolism (VTE) than the general population. Novel oral anticoagulants (NOACs) provide convenient alternatives to traditional therapies.

Methods: We performed a systematic literature search across PubMed, Embase, and the Cochrane Library, targeting studies that examined the use of NOACs in cancer-associated VTE. The search included randomized controlled trials (RCTs). Selected studies compared NOACs with low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKA) in cancer patients diagnosed with VTE. A meta-analysis using a random-effects model was applied to estimate pooled effect sizes for outcomes.

Results: In this meta-analysis, we included 12 RCTs. Results showed NOACs were more effective than LMWH in preventing VTE recurrence (RR 0.66, 95% CI 0.52-0.83, p = 0.0004). Compared with VKAs, NOACs showed no significant difference (RR 0.63, 95% CI 0.34-1.15, p = 0.13). However, this finding is limited by the small patient sample. Major bleeding outcomes were similar between NOACs and LMWH/VKAs (RR 1.24, 95% CI 0.85-1.80, p = 0.28; RR 0.77, 95% CI 0.39-1.53, p = 0.46, respectively). Meta-regression analysis indicated a statistically significant positive correlation between mortality and major bleeding events when comparing NOACs with LMWH (p = 0.049). There was no significant difference in all-cause mortality between patients treated with NOACs and those treated with LMWH (RR 1.04, 95% CI 0.92-1.18, p = 0.54) or VKAs (RR 0.94, 95% CI 0.72-1.23, p = 0.65).

Conclusion: Meta-analysis shows NOACs, especially factor Xa inhibitors, reduce VTE recurrence in cancer patients more effectively than LMWH. Comparison between NOACs and VKAs is inconclusive due to limited patient data. Further research is needed to assess NOACs' efficacy and safety against VKAs.

Levosimendan, a Ca2 + sensitizer with positive inotropic effects, is primarily employed for the short-term treatment of acute decompensated heart failure (ADHF). Levosimendan exerts renal function protection through various mechanisms, including anti-apoptosis, anti-inflammatory, and antioxidant effects in vivo. Additionally, levosimendan may have a protective effect on individuals with heart failure and renal insufficiency, as well as on renal function impairment after cardiac surgery. However, the application of levosimendan in patients with severe renal dysfunction remains controversial. This article delves into the use of levosimendan in severe renal insufficiency, explores its impact on renal function, and provides a comprehensive overview of its impact on renal function after cardiac surgery.

Purpose: Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM), and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer.

Methods: Patients ≥ 18 years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new-onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over 2 years from HT initiation.

Results: After propensity score matching, 2155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (OR 0.539, 95% CI 0.446-0.651; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations, and all-cause mortality.

Conclusions: Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal, and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.

Objective: Cardiovascular diseases (CVDs) are major public health problems that threaten the lives and health of individuals. The article has reviewed recent progresses about ferroptosis and ferroptosis-related intervention approaches for the treatment of CVDs and provided more references and strategies for targeting ferroptosis to prevent and treat CVDs.

Methods: A comprehensive review was conducted using the literature researches.

Results and discussion: Many ferroptosis-targeted compounds and ferroptosis-related genes may be prospective targets for treating CVDs and our review provides a solid foundation for further studies about the detailed pathological mechanisms of CVDs.

Conclusion: There are challenges and limitations about the translation of ferroptosis-targeted potential therapies from experimental research to clinical practice. It warrants further exploration to pursure safer and more effective ferroptosis-targeted thereapeutic approaches for CVDs.