Journal of Cardiovascular Pharmacology最新文献

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.

Research objective: This study explored the effects of long-term cold stress on aortic vascular function in guinea pigs. Research Methods: Hartley guinea pigs (n=32) were divided into following groups: atherosclerosis (AS), cold stress (CS), and menthol-stimulated (M) and control (C). On days 1, 15, 30, 45, and 60, guinea pigs in the AS, CS, and M groups were intraperitoneally injected with bovine serum albumin. The C group was provided with maintenance feed and room-temperature water. The AS group was provided with a high-fat diet and room-temperature water. The CS group was maintained in a refrigerator at 4 °C，while providing a high-fat diet and iced water. The M group was administered menthol solution, and provided with a high-fat diet and room-temperature water. The modeling period lasted for 120 days. On day 121, abdominal aortic sera and aortic samples were obtained after intraperitoneal injection of sodium pentobarbital. Blood rheology tests were conducted to assess blood adhesion, biochemical tests to assess lipid levels, and enzyme-linked immunosorbent assays to detect serum nuclear factor-κB, tumor necrosis factor-α, and interleukin-1β, and endothelial nitric oxide (NO) synthase, NO, and endothelin-1(ET-1) in aortic tissue. Hematoxylin and eosin and Oil Red O staining were used to examine pathologic changes in the aorta, western blotting to detect TRPM8 and PKG protein expression, qPCR was used to measure VCAM-1 mRNA expression level. Research findings: Prolonged exposure to cold stress exacerbated lipid-metabolism disorders in guinea pigs fed a high-fat diet, increased aortic vascular cell adhesion, and exacerbated vascular inflammation, leading to endothelial injury, ultimately worsening pathologic changes associated with aortic atherosclerosis.

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.

Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and angiotensin receptor-neprilysin inhibitor (ARNI) may cause potential renal damage, the combined impact of SGLT2Is and ARNI on acute kidney injury (AKI) remains unclear. This pharmacovigilance study conducted a disproportionality analysis using reports from the FAERS database. The reporting odds ratio (ROR) was used as an estimate for detecting AKI signal. A total of 659,573 reports on at least one glucose-lowering drug and/or ARNI were obtained. Of the 413 reports on co-therapy of SGLT2Is and ARNI, 99 (24.0%) reports mentioned AKI. Overall, the AKI reporting rate significantly increased in co-therapy (adjusted ROR, 95%CI:8.04, 6.20-10.42, P<0.001), with a stronger AKI signal in co-therapy of canagliflozin and ARNI (16.82, 3.75-75.57, P<0.001). Specifically, no increased AKI signal was detected in HF cases receiving co-therapy after adjustment for sex and age (HF:1.27, 0.89-1.80, P=0.189; HF plus diabetes:2.08, 0.99-4.40, P=0.055; or HF plus hypertension:1.69, 0.53-5.35, P=0.376), whereas enhanced AKI signals were detected in cases with diabetes (20.57, 11.93-35.46, P<0.001), hypertension (4.30, 1.98-9.37, P<0.001), or diabetes plus hypertension (5.44, 1.92-15.43, P=0.001). This study reveals that superimposed renal impairment results from co-therapy with SGLT2Is and ARNI. It is necessary to be vigilant that the elderly, patients with diabetes, hypertension or CKD are more susceptible to AKI, especially if they likewise receive diuretics. When co-therapy is unavoidable, early monitoring of renal function, blood volume and blood pressure is excessively crucial. However, it is relatively safe in HF patients.