Journal of Cardiovascular Pharmacology最新文献

Patient-reported outcome measures (PROMs) are vital tools in cardiovascular disease (CVD) research and care, providing insights that complement traditional clinical outcomes like mortality and morbidity. PROMs capture patient experiences with CVD, such as quality of life, functional capacity, and emotional well-being, allowing clinicians to assess how interventions impact daily life. PROMs are integral to cardiovascular investigations as well as management, especially in chronic conditions and rehabilitation, where they inform on the impact of personalized care plans by tracking symptom progression and patient adherence. Selecting and applying to cardiovascular research and practice effective PROMs involves evaluating their validity, reliability, and sensitivity to change, with instruments like the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Seattle Angina Questionnaire (SAQ) widely used for heart failure and coronary artery disease, respectively. Implementing PROMs in real-world practice requires addressing challenges related to workflow integration and patient adherence, emphasizing their value in patient-centered care. As digital health advances, remote PROM data collection through mobile applications and wearable devices will enhance access to and extent of PROMs, and AI-driven analytical tools will provide real-time, automated and plausible more poignant insights for personalized treatment. Future efforts should focus on culturally adapting PROMs for diverse populations to ensure global applicability. PROMs should also be established as essential components of innovative research and responsive, patient-centered cardiovascular care.

Receptors for the vasoactive adipokine apelin, termed APJ receptors, are G-protein-coupled receptors and are widely expressed throughout the cardiovascular system. APJ receptors can also signal via G-protein-independent pathways, including G-protein-coupled-receptor kinase 2 (GRK2), which inhibits nitric oxide synthase (eNOS) activity and nitric oxide (NO) production in endothelial cells. Apelin causes endothelium-dependent, NO-mediated relaxation of coronary arteries from normotensive animals, but the effects of activating APJ receptor signaling pathways in hypertensive coronary arteries are largely unknown. We hypothesized that apelin-induced relaxation is impaired in coronary arteries from spontaneously hypertensive rats (SHR). Western blot and mRNA analysis revealed increased GRK2 expression in cultured SHR coronary endothelial cells. Apelin failed to cause relaxation in isolated SHR coronary arteries but, in the presence of apelin, relaxations to acetylcholine (ACh) were impaired. Apelin had no effect on relaxation to DEA NONOate. The GRK2 inhibitor, CMPD101, increased apelin-induced phosphorylation of Akt and eNOS in SHR endothelial cells and restored relaxation to apelin in SHR arteries. CMPD101 also blocked the inhibitory effect of apelin on ACh-induced relaxation. Relaxations to the APJ receptor-biased agonist, CMF-019, which preferentially activates the G-protein-dependent pathway with minimal effect on GRK2, were similar in SHR and WKY coronary arteries. Immunoblot analysis in SHR coronary endothelial cells demonstrated that CMF-019 increased Akt and eNOS phosphorylation whereas apelin had no effect. Thus, APJ receptor signaling via GRK2 impairs NO production or release from SHR endothelial cells. APJ receptor-biased agonists, such as CMF-019, may be more effective than apelin in causing vasodilation of SHR coronary arteries.

Abstract: 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 nonselective cationic channels, although our knowledge of these channels is still inadequate. The transient receptor potential (TRP) superfamily comprises of many nonselective 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 signaling 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 was 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.

Abstract: Lisinopril is commonly prescribed to manage conditions such as hypertension and heart failure. Although concerns about fetal toxicity have traditionally limited the use of lisinopril in women of reproductive age, recent American College of Obstetricians and Gynecologists 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 through breast milk 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 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.

Abstract: 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 3 distinct forms of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy. In the heart, autophagy is regulated mainly through mitophagy because of 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.

Abstract: The clinical effect of drug-drug interactions (DDIs) between antiplatelets and antiretroviral therapy (ART) on bleeding, thrombosis, and other major adverse cardiovascular events (MACE) is unknown. The objective of this retrospective study was to assess the incidence of DDI at P2Y12 inhibitor (P2Y12inh) initiation and the effect of DDI on patient outcomes. Adult people living with HIV (PLWH) receiving ART newly initiated on an oral P2Y12inh were included. The primary outcome was the incidence of DDI between ART and P2Y12inh at P2Y12inh initiation. Secondary outcomes included bleeding events, MACE, and switches in P2Y12inh. There were 149 PLWH included, of these, 119 (80%) were initiated on clopidogrel, 23 (15%) on ticagrelor, and 7 (5%) on prasugrel. Ninety-three PLWH (60%) had a DDI at time of P2Y12inh initiation, with highest incidence in the clopidogrel group (n = 84, 71%), followed by ticagrelor (n = 9, 39%) and none with prasugrel. Within 1 year, MACE occurred in 12 PLWH, with DDI present at the time of 4 events. There were 29 bleeding events occurring within 1 year, including 17 events with DDI at time of event. However, 88% of DDI in patients with bleeding events were expected to decrease the efficacy of P2Y12inh. Though we observed high incidence of DDI between P2Y12inh and ART in PLWH, MACE and bleeding events at 1 year did not correlate with DDI. It remains unknown whether DDI presence at P2Y12inh initiation with ART causes clinical outcomes of concern, or whether underlying platelet reactivity in PLWH is associated with these events.

Abstract: 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 FDA Adverse Event Reporting System database. The reporting odds ratio was used as an estimate for detecting AKI signal. A total of 659,573 reports on at least 1 glucose-lowering drug and/or ARNI were obtained. Of the 413 reports on cotherapy of SGLT2Is and ARNI, 99 (24.0%) reports mentioned AKI. Overall, the AKI reporting rate significantly increased in cotherapy (adjusted reporting odds ratio, 95% confidence interval: 8.04, 6.20-10.42, P < 0.001), with a stronger AKI signal in cotherapy of canagliflozin and ARNI (16.82, 3.75-75.57, P < 0.001). Specifically, no increased AKI signal was detected in patients with heart failure (HF) receiving cotherapy 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 patients 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 cotherapy with SGLT2Is and ARNI. It is necessary to be vigilant that the elderly patients with diabetes, hypertension, or chronic kidney disease are more susceptible to AKI, especially if they likewise receive diuretics. When cotherapy is unavoidable, early monitoring of renal function, blood volume, and blood pressure is excessively crucial. However, it is relatively safe in patients with HF.

Abstract: Renin-angiotensin system inhibitors (RASis), specifically angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs), are widely used antihypertensives. Their impact on the prognostic outcomes among patients with cancer has been subject to scrutiny and debate. The aim of this study was to evaluate the effect of RASis on survival in patients with cancer.We systematically searched PubMed, Web of Science, Embase, and Cochrane Library for relevant studies published until April 1, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEis on cancer prognosis compared with a control group and reported the survival outcomes and hazard ratios were included in the analysis. From each study, pooled hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity.61 studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASis improved overall survival (HR = 0.88; 95% CI, 0.82-0.93; P < 0.0001), progression-free survival (HR = 0.72; 95% CI, 0.65-0.79; P < 0.00001), disease-specific survival (HR = 0.86; 95% CI, 0.71-1.04; P = 0.03), and recurrence-free survival (HR = 0.74; 95% CI, 0.58-0.93; P = 0.01) in patients with cancer. The effect of RASis on overall survival varied depending on the type of cancer or type of RASis (ACEis or ARBs), according to subgroup analysis.The usage of renin-angiotensin system inhibitors has a positive impact on survival outcomes and recurrence among patients with cancer.

Heart failure (HF) has become even more prevalent in recent years, because of improved diagnostics and an increase in the risk factors predisposing to its pathology. Sodium-glucose cotransporter 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 pathophysiologic 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 because observations of retained or reduced heart rate 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, although 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 pharmacologic and interventional therapies, in this review, we aim to describe the role of SNS in CV disease, focusing on HF, analyze preclinical and clinical data regarding the efficacy of SGLT2i in modulating autonomic dysfunction by examining various markers of SNS activation, and provide the most plausible theoretical backgrounds on the mechanism of benefit of SNS from the inhibition of SGLT2 receptors.