Journal of Cardiovascular Pharmacology最新文献

Abstract: Ischemic heart disease gravely threatens human health and even results in death. Kirenol is predominantly derived from the Herba Siegesbeckiae plant species and possesses a wide range of biological effects (such as antibacterial, anti-inflammatory, anticancer, and cardioprotective). However, the regulatory effects and associated mechanisms of kirenol in myocardial ischemia/reperfusion injury (MI/RI) remain unclear. In this study, first, the MI/RI rat model was established. It was demonstrated that kirenol protected against the aggravation of cardiac function in MI/RI rats. In addition, the inflammation was induced by ischemia reperfusion (IR), which was likewise affected by kirenol (5 or 10 mg/kg). Moreover, IR enhanced oxidative stress, a process that was counteracted by kirenol. Next, cell apoptosis was discovered to be heightened after IR, but this effect was neutralized by kirenol. Finally, it was revealed that kirenol has the ability to block the activation of the NF-κB pathway. In conclusion, it was disclosed that kirenol alleviated inflammation and oxidative stress through modulating the NF-κB pathway to improve MI/RI in rats. This work may offer novel insights for searching useful drugs for treating MI/RI.

Abstract: The aim of this study was to explore the incidence of new-onset erectile dysfunction (ED) in diabetes mellitus (DM) patients with sodium-glucose cotransporter 2 inhibitors (SGLT2I) use compared with a control group of non-SGLT2I use by propensity score matching approach. Cox proportional hazards regression models were used to examine the effect of SGLT2I and risk factors on the risk of developing ED, presented as a hazard ratio with a 95% confidence interval. One lakhs fifty nine thousand seven hundred seventy three patients with DM using SGLT2I and 159,773 propensity score matching patients with DM who had never used SGLT2I were included. SGLT2I users had a higher risk of ED than the non-SGLT2I users (adjusted hazard ratio = 1.55, 95% confidence interval = 1.40-1.72). The likelihood of developing ED was higher in patients with SGLT2I use was found.

Abstract: Patients undergoing anthracycline-based cancer treatments have an increased risk of heart failure or worsening preexisting heart failure as well as adverse metabolic outcomes such as malnutrition and cachexia. This retrospective study explored the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in patients with heart failure previously treated with anthracyclines. Using the TriNetX research network, we identified 1545 patients with a history of SGLT2i use and 17,681 patients without a history of SGLT2i use. We then performed 1:1 propensity score matching resulting in 1323 patients within each cohort. Patients were analyzed over a 5-year period. SGLT2i use was associated with significantly reduced risks of cachexia {hazard ratio (HR) 0.453, 95% confidence interval (CI) [0.286-0.718]}, malnutrition (HR 0.702, 95% CI [0.547-0.900]), adult failure to thrive (HR 0.489, 95% CI [0.345-0.693]), and all-cause mortality (HR 0.490, 95% CI [0.423-0.568]). These findings call for additional research to determine whether SGLT2i may indeed improve nutritional status and survival in patients with heart failure receiving anthracycline therapy.

Autophagy is the process of reusing the body's senescent and damaged cell components, which can be regarded as the cellular circulatory system. There are three distinct forms of autophagy: macro-autophagy, micro-autophagy, and chaperone-mediated autophagy. In the heart, autophagy is regulated mainly through mitophagy due to the metabolic changes of cardiomyocytes caused by ischemia and hypoxia. Myocardial remodeling is characterized by gradual heart enlargement, cardiac dysfunction, and extraordinary molecular changes. Cardiac remodeling after myocardial infarction is almost inevitable, which is the leading cause of heart failure. Autophagy has a protective effect on myocardial remodeling improvement. Autophagy can minimize cardiac remodeling by preventing misfolded protein accumulation and oxidative stress. This review summarizes the nestest molecular mechanisms of autophagy and myocardial remodeling, the protective effects, and the new target of autophagy medicine in cardiac remodeling. The future development and challenges of autophagy in heart disease are also summarized.

Heart failure (HF) has become even more prevalent in recent years, as a result of improved diagnostics and an increase in the risk factors predisposing to its pathology. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) emerged as one of the key pharmacotherapy options for both reduced and preserved ejection fraction, providing cardio- and renoprotection and improving mortality and cardiovascular (CV) outcomes. The pleiotropism of SGLT2i has led to multiple efforts to understand their distinct pathophysiological interactions with various pathways, including microcirculation, endothelial dysfunction, and inflammation. More recently, the role of SGLT2i on the sympathetic nervous system (SNS) is starting to be recognized, especially as observations of retained or reduced heart rate (HR) despite volume contraction have been noted by investigators in the large clinical trials testing the safety and efficacy of these agents. Both preclinical and clinical studies have been performed, with conflicting results. Interestingly, in both settings, whilst there are indications of SNS modulation by SGLT2i, other studies contradict such findings, without showing, however, worsening of the autonomic homeostasis. Given the importance of neuromodulation in HF, in both pharmacological and interventional therapies, in this review, we aim to describe the role of SNS in CV disease, focusing on HF, analyse preclinical and clinical data regarding the efficacy of SGLT2i in modulating autonomic dysfunction by examining various markers of SNS activation, as well as provide the most plausible theoretical backgrounds on the mechanism of benefit of SNS from the inhibition of SGLT2 receptors.

Cardiac hypertrophy is a crucial risk factor for heart failure when the heart is confronted with physiological or pathological stimuli. The ubiquitin-proteasome system (UPS) plays a critical role in the pathogenesis of cardiac hypertrophy. However, as a key component of the UPS, the role of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is not well understood. Here, we observed that the expression level of deubiquitinase USP47 was increased in hypertrophic hearts and angiotensin II (Ang II)-stimulated neonatal rat cardiomyocytes (NRCMs). Adenovirus-mediated gain- and loss-of-function approaches indicated that USP47 overexpression significantly attenuated Ang II-induced cardiac hypertrophy in vitro and in vivo, whereas endogenous USP47 deficiency promoted the pro-hypertrophic effect of Ang II. Further investigation demonstrated that USP47 inhibited O-GlcNAcylation in cardiomyocytes by controlling the expression of O-GlcNAcase (OGA). Mechanistically, USP47 bound, deubiquitinated, and stabilized protein arginine methyltransferase 5 (PRMT5), thus upregulating OGA expression. We found that the restoration of PRMT5 abolished the pro-hypertrophic effects of USP47 silence in vitro. Therefore, our results provide the first evidence of the involvement of USP47 in cardiac hypertrophy and identify USP47 as a potential target for hypertrophic therapy.

Lisinopril is commonly prescribed to manage conditions such as hypertension and heart failure. While concerns about fetal toxicity have traditionally limited the use of lisinopril in women of reproductive age, recent ACOG guidelines promote aggressive treatment of hypertension, which may require the use of pharmacologic agents not previously considered in the postpartum period. We aimed to estimate infant exposure to maternal lisinopril via breastmilk and report the tolerance of the breastfed infant. Five volunteers taking lisinopril provided samples of their human milk and their associated health information for research through the InfantRisk Center Human Milk Biorepository. The milk pharmacokinetics of lisinopril were measured using liquid chromatography-mass spectrometry. The mean milk concentration of lisinopril was 0.49 ng/mL per 10 mg daily dose. The Relative Infant Dose (RID) was 0.06% for lisinopril, more than 100 times lower than the standard 10% safety threshold. The minimal transfer of lisinopril into human milk in this study suggests the drug is unlikely to pose a clinically significant risk to healthy breastfed infants.

Ion channels play a crucial role in various aspects of cardiac function, such as regulating rhythm and contractility. As a result, they serve as key targets for therapeutic interventions in cardiovascular diseases. Cell function is substantially influenced by the concentration of free cytosolic calcium (Ca 2+ ) and the voltage across the plasma membrane. These characteristics are known to be regulated by Ca 2+ -permeable non-selective cationic channels, although our knowledge of these channels is still inadequate. The transient receptor potential (TRP) superfamily comprises of many non-selective cation channels with diverse Ca 2+ permeability. Canonical or classical TRP (TRPC) channels are a subgroup of the TRP superfamily that are expressed ubiquitously in mammalian cells. TRPC channels are multidimensional signalling protein complexes that play essential roles in a variety of physiological and pathological processes in humans, including cancer, neurological disorders, cardiovascular diseases, and others. The objective of this article is to focus on the role that TRPC channels play in the cardiovascular system. The role of TRPC channels will be deeply discussed in cardiovascular pathology. Together, a critical element in developing novel treatments that target TRPC channels is comprehending the molecular mechanisms and regulatory pathways of TRPC channels in related cardiovascular diseases and conditions.

Patients with atrial fibrillation (AF) taking antithrombotic (AT) therapy are at increased risk of gastrointestinal bleeding (GIB). The comparative effect of a combination of anticoagulant (AC) and antiplatelet (AP) versus AC monotherapy on clinical outcomes in patients with AF presenting with GIB is not well characterized. This study compares outcomes in AF patients with GIB on AC alone to those on combination AP and AC therapy, as part of a larger prospective study from 2013 to 2023. 137 patients diagnosed with AF who presented with overt GIB were evaluated during their hospitalization, at one month and one year post-discharge, and then annually. The median follow-up of patients was 57 months. Patients in the combination AP +AC therapy group had a higher prevalence of CAD, myocardial infarction, and coronary/vascular stent placement compared to the AC monotherapy group. No statistically significant differences were noted between the two groups in terms of end-of-follow-up mortality, in-hospital mortality, major bleeding, rebleeding, and length of hospital stay. Cox regression analysis revealed chronic kidney disease (CKD) (hazard ratio (HR) 2.05, 95% confidence interval (CI) [1.04,4.05] (p= 0.038)] and warfarin use [(HR 4.94, 95% CI [1.11,22.09] (p= 0.037)] to be independent predictors of mortality at 12 months. Anti-thrombotic therapy in patients with AF who experience GIB should be mainly directed by their cardiovascular needs. Healthcare providers may explore non-vitamin K antagonist oral anticoagulants as alternatives to warfarin for AF patients at risk of GIB, and efforts must be maximized to prevent bleeding in patients with CKD.