Cardiovascular Drugs and Therapy最新文献

Purpose: Inflammatory responses induced by NLRP3 inflammasome contribute to the progression of atherosclerosis. This study seeks to investigate the effect of emodin on the NLRP3 inflammasome in atherogenesis and to probe the underlying mechanism.

Methods: ApoE-knockout (ApoE^-/-) mice were treated with a high-fat diet (HFD) for 12 weeks and intragastrically with emodin for 6 weeks. Human mononuclear cell line THP-1 was pretreated with emodin or signaling pathway inhibitors and induced into macrophages using phorbol 12-myristate 13-acetate (PMA) for 48 h. The NLRP3-mediated inflammatory response was studied both in vivo and in vitro. The level of the inflammation was detected by western blot, real-time PCR analysis, and ELISA.

Results: Emodin attenuated atherosclerotic lesions in HFD-treated ApoE^-/- mice. Emodin dramatically decreased the expression of NLRP3, GSDMD, IL-1β, and IL-18 in HFD-treated ApoE^-/- mice and PMA-induced macrophages. Moreover, emodin significantly hindered the activation of nuclear factor kappa-B (NF-κB) by inhibiting the formation of the TLR4/MyD88 complex in PMA-induced macrophages.

Conclusion: Our data demonstrate that emodin can inhibit the development of atherosclerotic plaques by alleviating NLRP3/GSDMD-induced inflammation through repressing the TLR4/MyD88/NF-κB signaling pathway in macrophages. This finding suggests that emodin can be a potential candidate for the treatment of atherosclerosis.

Purpose: Heme oxygenase-1 (HO-1) is a crucial enzyme in heme metabolism, facilitating the breakdown of heme into biliverdin, carbon monoxide, and free iron. Renowned for its potent cytoprotective properties, HO-1 showcases notable antioxidant, anti-inflammatory, and anti-apoptotic effects. In this review, the authors aim to explore the profound impact of HO-1 on cardiac senescence and its potential implications in myocardial infarction (MI).

Results: Recent research has unveiled the intricate role of HO-1 in cellular senescence, characterized by irreversible growth arrest and functional decline. Notably, cardiac senescence has emerged as a pivotal factor in the development of various cardiovascular conditions, including MI. Notably, cardiac senescence has emerged as an important factor in the development of various cardiovascular conditions, including myocardial infarction (MI). The accumulation of senescent cells, spanning vascular endothelial cells, vascular smooth muscle cells, cardiomyocytes, and progenitor cells, poses a significant risk for cardiovascular diseases such as vascular aging, atherosclerosis, myocardial infarction, and ventricular remodeling. Inhibition of cardiomyocyte senescence not only reduces senescence-associated inflammation but also impacts other myocardial lineages, hinting at a broader mechanism of propagation in pathological remodeling. HO-1 has been shown to improve heart function and mitigate cardiomyocyte senescence induced by ischemic injury and aging. Furthermore, HO-1 induction has been found to alleviate H₂O₂-induced cardiomyocyte senescence. As we grow in our understanding of antiproliferative, antiangiogenic, anti-aging, and vascular effects of HO-1, we see the potential to exploit potential links between individual susceptibility to cardiac senescence and myocardial infarction.

Conclusions: This review investigates strategies for upregulating HO-1, including gene targeting and pharmacological agents, as potential therapeutic approaches. By synthesizing compelling evidence from diverse experimental models and clinical investigations, this study elucidates the therapeutic potential of targeting HO-1 as an innovative strategy to mitigate cardiac senescence and improve outcomes in myocardial infarction, emphasizing the need for further research in this field.

Background: Ivabradine has been identified as a funny current (If) inhibitor in the sinoatrial node (SAN) and is considered an advocated therapeutic agent in chronic heart failure and stable angina. This therapeutic agent has shown positive benefits in maintaining a reduction in heart rate while sustaining hemodynamic stability. Its clinical application is still evolving and the mechanism of action is becoming clearer daily. The use of this agent to manage atrial fibrillation (AF) has recently been brought under discussion. This study summarizes the mechanism of action of ivabradine and current evidence about the risk of new-onset AF and rate-lowering potential as a therapeutic option in patients suffering from AF.

Methods: This review synthesizes findings from preclinical studies, case reports, and clinical trials that assess ivabradine's efficacy in controlling heart rate and its association with new-onset AF.

Results: Studies have shown that this medication may be beneficial in ventricular rate reduction in patients intolerant of first-line AF therapeutic options, including non-dihydropyridine calcium channel blockers and β-blockers. However, it is important to state that ivabradine-treated patients with cardiovascular diseases demonstrated an increased risk for new-onset AF compared with those patients who did not receive it.

Conclusion: While ivabradine demonstrates promise as a therapeutic option for rate control in patients with AF, its use is accompanied by a notable risk of new-onset AF. Further studies should focus on optimal dosing strategies and long-term outcomes of ivabradine treatment in AF management.

Several reports suggest that in animal models, as well as in the clinical setting, long-term warfarin use increases coronary artery calcifications. The same has been reported for statins prescribed for patients at risk or with established atherosclerosis. Coronary calcifications are considered a risk marker for further cardiovascular events. However, numerous clinical trials have established that statins reduce the risk for cardiovascular events. Warfarin also has been shown to reduce the risk of cardiovascular events, including re-infarction. It has been suggested that the increase in coronary calcification can be viewed as a marker of stabilization of the coronary plaque in such patients. Warfarin inhibits the activation of Vitamin K epoxide reductase complex 1 (VKORC1), which blocks the regeneration of reduced vitamin K1 and K2. Vitamin K1 is predominantly localized to the liver, serving to carboxylate clotting factors. Vitamin K2 travels through systemic circulation, with significant and wide-ranging effects. Several studies using animal models of atherosclerosis have shown that vitamin K2 supplement can attenuate the progression of atherosclerosis, as well as coronary calcification. Clinical studies supporting this effect in patients are lacking. Yet, there is an increase in the use of over-the-counter vitamin K2 supplements, and several manuscripts recommended its use in patients receiving long-term warfarin to attenuate coronary calcification. However, it is unclear if this occurs in patients with atherosclerosis receiving warfarin or statins and if attenuating coronary calcification has beneficial or detrimental effects on cardiovascular outcomes.

Purpose: Proton pump inhibitors (PPIs) are widely prescribed for gastrointestinal disorders. Lansoprazole, a PPI, has been recognized for its potential effects of improving insulin resistance, reduction of oxidative stress, and improvement in atherosclerosis through peroxisome proliferator-activated receptor gamma (PPARγ) induction. This study aims to investigate whether lansoprazole poses a distinct risk of coronary heart disease (CHD) compared to other PPIs.

Methods: A retrospective cohort study utilized data from the National Health Insurance Research Database in Taiwan spanning from 2000 to 2013. The exposed cohort included 1666 patients with lansoprazole use, while the comparison cohort comprised 6664 patients using other PPIs. The primary outcome was incident CHD. Cox regression models were employed to assess the association between lansoprazole use and CHD risk, presenting hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Patients prescribed lansoprazole demonstrated a significantly reduced risk of CHD compared to those undergoing other PPI treatments in individuals without a history of CHD. Lansoprazole users exhibited a 25% lower risk of developing CHD compared to other PPI users (adjusted HR 0.75; 95% CI 0.65-0.87). Intriguingly, this inverse association between lansoprazole use and CHD risk was consistent across genders and various age groups.

Conclusion: This study suggests that lansoprazole is associated with a decreased risk of CHD in comparison to other PPIs in patients without a history of CHD. Further research is warranted to elucidate the clinical implications of these findings.

We appreciate the thoughtful commentary by Drs. Dziewierz and Siudak regarding our study comparing tirzepatide versus semaglutide in post-CABG diabetic patients. While we acknowledge the inherent limitations of observational research, our propensity score matching achieved near-perfect balance across 40+ covariates (SMD = 0.033), including comprehensive medication proxies for diabetes control, lipid management, and blood pressure control. We observed consistent protective effects across multiple distinct outcome domains-cerebrovascular, cardiovascular, thrombotic, mortality, and healthcare utilization-with nine outcomes significant after Benjamini-Hochberg correction. The cerebrovascular benefit is particularly noteworthy given semaglutide's neutral stroke effect in SELECT trial, suggesting differential GIP receptor-mediated neurovascular protection. SURPASS-CVOT, comparing tirzepatide to dulaglutide (not semaglutide) in general ASCVD populations, addresses a different clinical question and may lack power for post-CABG subgroup analysis. Our findings provide hypothesis-generating evidence for an understudied high-risk population, warranting further investigation in dedicated trials.

Purpose: Pulmonary hypertension (PH) is a clinicopathological syndrome characterized by structural and functional alterations in the pulmonary vasculature arising from heterogeneous etiologies (including hypoxia) and diverse pathogenic mechanisms. These changes elevate pulmonary vascular resistance and increase pulmonary arterial pressure, ultimately progressing to right heart failure and potential fatality. Resistin-like molecule (RELM)-β activates multiple signaling pathways. This study aimed to explore the role of RELM-β in the development of chronic hypoxia-induced PH and its potential mechanisms.

Methods: Exogenous human RELM-β was injected into a mouse model of hypoxia for 3 weeks, followed by histological and hemodynamic analyses. The relationship between RELM-β and membrane proteins or receptors (OR1N1, GIPC1 and CLIC4) was determined by affinity purification-mass spectrometry (AP-MS) and co-immunoprecipitation. At the same time, in vitro cell culture experiments were carried out.

Results: Cell membrane proteins or receptors (OR1N1, GIPC1, and CLIC4) were identified as proteins interacting with RELM-β and potentially involving in the development of PH. Compared with the RELM-β overexpression group, siRNA-mediated silencing of OR1N1, GIPC1, or CLIC4 resulted in significant reduction of cell viability in both human pulmonary artery smooth muscle cells (PASMCs) and human pulmonary arterial endothelial cells (PAECs). Moreover, augmenting effect of exogenous RELM-ß on the hypoxia-induced PH was remarkably reduced in the mice with genetic deficiency of GIPC1 (GIPC1 CKO) or CLIC4 (CLIC4 CKO) compared to the wild type mice.

Conclusions: Findings of the current study suggested that RELM-β may play an important role in the development of hypoxia-induced PH through interacting with membrane proteins or receptors, including GIPC1, OR1N1, and CLIC4.

Purpose: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure with preserved ejection fraction (HFpEF), yet comparative effectiveness between steroidal and nonsteroidal agents remains unknown. Our aim was to compare cardiovascular and safety outcomes associated with finerenone versus spironolactone among patients with HFpEF.

Methods: This retrospective cohort study used a global federated health research network to identify adults with new-onset HFpEF between January 1, 2021, and August 1, 2025. Propensity score matching (1:1) balanced baseline characteristics, and outcomes were assessed with Cox proportional hazards models. A total of 253 patients prescribed finerenone and 32,266 prescribed spironolactone were identified; after matching, 251 patients were retained in each cohort (mean age, 73 years; 47% female). The primary outcome was acute HF events. Secondary outcomes included all-cause hospitalizations, mortality, myocardial infarction, stroke, and a composite of major adverse cardiovascular events. Safety outcomes included acute kidney injury (AKI) and hyperkalemia.

Results: Acute HF events occurred in 6.0% of patients receiving finerenone and 4.4% receiving spironolactone (HR 1.26, 95% CI 0.58-2.74). All-cause mortality was lower with finerenone (4.4% vs. 8.0%; HR 0.48, 95% CI 0.23-1.00). Other clinical and safety outcomes, including MACE (11.6% vs. 10.8%), AKI (10.4% vs. 8.0%), and hyperkalemia (5.8% vs. 6.2%), were similar between groups.

Conclusion: In this first direct comparison of MRAs in HFpEF, finerenone demonstrated broadly comparable effectiveness and safety to spironolactone. While these observations are hypothesis-generating, prospective studies are warranted to confirm these findings and inform therapeutic decision-making.