Journal of Cardiovascular Pharmacology and Therapeutics最新文献

BackgroundThe therapeutic potential of the human amnion has been known since the early twentieth century. Subsequent study has revealed the further therapeutic potential of all elements of the amnion-membrane, cells, fluid-in the treatment of cardiac disease.Materials and MethodsA systematic review was performed utilizing PubMed/MEDLINE and Embase with search terms including "amniotic fluid," "cardiovascular disease," "cardiac disease," "amnion," "amniotic membrane," and "heart." Results were reviewed by each author to ensure inclusion of all relevant articles. Animal studies were included for evaluation of existing preclinical models, and the few available clinical studies of amniotic products were included.ResultsPreclinical studies addressing organ function, assessment, and enhancement of cardiac performance in response to injury, and regenerative potential are included, as are the few clinical studies utilizing amniotic products for the treatment of cardiac disease. Therapeutic approaches include reduction of inflammation, immunomodulation, and the promotion of myocardial regeneration via cellular therapy to target the most common mechanisms underlying myocardial injury.ConclusionsThe components of the human amnion have anti-inflammatory, immunomodulatory, and pro-differentiation abilities which lend the ability to attenuate myocardial ischemia-reperfusion injury, temper cardiac fibrosis, and promote activation of progenitor cells to induce regeneration. Preclinical studies have focused heavily on cellular therapy, but clinical experience has yielded little success. The acellular components of the amnion have fueled more recent investigation and represent a new source of enthusiasm for clinical translation of amniotic products in the treatment of cardiac disease.

BackgroundCardiovascular disease remains the first major reason for death in global, and hypertension is one very usual risk factor for this disease. Chemokine (CXC motif) ligand 13 (CXCL13) exhibits a crucial role in the development and angiogenesis of a variety of diseases. However, the impacts of CXCL13 in the amelioration of hypertension and the associated regulatory mechanisms have rarely reported.MethodsThe hypertensive rat model was induced by Ang II treatment. The protein and mRNA expressions were measured through western blot and RT-qPCR. The systolic blood pressure was monitored. The ET-1 level was examined through the commercial kit. The thickness of vascular elasticity layer was observed through hematoxylin eosin staining. The levels of angiotensin-converting enzyme (ACE), thiobarbituric acid-reactive substances (TBARS), and brain natriuretic peptide (BNP) were inspected through the commercial kits.ResultsCXCL13 exhibited high protein and mRNA expressions in hypertensive rat model. Knockdown of CXCL13 improved vascular remodeling and elevated blood pressure in hypertensive rat model. Moreover, suppression of CXCL13 protected heart in hypertensive rat model through declining the levels of ACE, TBARS, and serum BNP. Next, it was demonstrated that CXCL13 modulated the PF4V1/NF-κB pathway. Eventually, through rescue assays, it was proved that CXCL13 ameliorated hypertension through affecting PF4V1.ConclusionThis study manifested that knockdown of CXCL13 improved vascular remodeling, reduced blood pressure, and protected the heart by affecting the PF4V1/NF-κB signaling pathway in a hypertensive rat model. This discovery may offer novel opinions in the treatment of hypertension.

BackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated significant cardiovascular benefits in clinical trial. While their role in reducing heart failure hospitalizations and cardiovascular mortality is well established, the precise mechanisms underlying their direct cardiac effects remain unclear. This literature review aims to synthesize current knowledge on the molecular and physiological pathways by which SGLT2 inhibitors may exert effects on cardiac tissue, independent of glycemic control.MethodsA comprehensive review of peer-reviewed articles, randomized controlled trials, meta-analyses, and mechanistic studies published in PubMed and related databases was conducted. The search focused on studies examining the direct impact of SGLT2 inhibitors on cardiac function, remodeling, metabolism, and intracellular signaling pathways. Only studies evaluating the cardiac effects separate from their glucose-lowering action were included in the analysis.ResultsThis review identified several key mechanisms by which SGLT2 inhibitors may benefit the heart directly, including reductions in oxidative stress, inflammation, and myocardial fibrosis. Emerging evidence suggests that these drugs modulate key pathways such as sodium-hydrogen exchange (NHE) inhibition, improvement of mitochondrial function, and promotion of ketone body utilization in cardiomyocytes.ConclusionsSGLT2 inhibitors appear to confer direct cardioprotective effects. These include anti-inflammatory, anti-fibrotic, and energy efficiency improvements in the myocardium. The findings highlight new potential therapeutic mechanisms and provide a foundation for further research into the non-diabetic use of SGLT2 inhibitors in heart failure and other cardiac conditions. Understanding these direct effects could lead to optimized treatment strategies for patients with and without diabetes.

PurposeDemonstration of the role of autocrine motility factor receptor (AMFR) in atrial fibrillation (AF) mice.MethodsThe AF model was established by administering Ang II to mice and transfected with AMFR knockdown or AMFR overexpression plasmids by tail vein injection of the AAV vector. Atrial fibrosis was examined by Masson staining. The mRNA expression of inflammatory factors TNF-α, IL-1β, and IL-6 in atrial tissue was detected by PCR. Reactive oxygen species (ROS) production in atrial tissue was examined by dihydroethidium staining. Apoptotic cells of atrial tissue were examined by TUNEL staining. The expression levels of fibrosis-related genes (COL1A1 and α-SMA), apoptosis-related genes (cleaved-caspase3 and cleaved-PARP), and SOD1 were detected by western blot. The ubiquitination level of superoxide dismutase 1 (SOD1) was detected by ubiquitination assay.ResultsAng II resulted in increased AMFR expression in mouse atrial tissue, and knockdown of AMFR inhibited atrial fibrosis, inflammatory factors, and ROS production, as well as apoptosis in mice. In addition, the knockdown of AMFR inhibited the ubiquitination level of SOD1 and increased the protein expression level of SOD1, whereas overexpression of AMFR exerted the opposite effect and aggravated Ang II-induced AF.ConclusionKnockdown of AMFR promotes SOD1 expression by inhibiting SOD1 ubiquitination levels and attenuates atrial fibrosis in AF mice by regulating SOD1.

Hypopituitarism, resulting from a partial or complete deficiency of anterior or posterior pituitary hormones, is associated with increased cardiovascular (CV) morbidity and mortality. This heterogeneous endocrinological disorder may arise from various etiologies, including genetic mutations, pituitary tumors, traumatic brain injury, and autoimmune diseases. Hypopituitarism often results in multiple endocrine deficits that contribute to metabolic dysregulation characterized by insulin resistance, dyslipidemia, and increased visceral adiposity, all known risk factors for CV disease (CVD). Additionally, the presence of chronic inflammation and endothelial dysfunction further increases the risk of CVD in these patients. While standard hormone replacement therapy (HRT) is crucial for restoring hormonal balance, it can sometimes have adverse metabolic effects that can exacerbate atherosclerosis and CVD. Emerging evidence suggests that optimizing HRT regimens and addressing specific hormone deficiencies, such as growth hormone and cortisol, may reduce these risks and improve CV outcomes. This review comprehensively analyzes the etiology, pathophysiological mechanisms underlying CV risk in anterior pituitary dysfunction, and treatment strategies to mitigate CV morbidity and mortality in patients with hypopituitarism.

BackgroundClopidogrel is a pro-drug that requires metabolic activation by hepatic cytochrome P450 (CYP) enzymes in two steps. Previous studies have shown that the administration of continuous nitrate significantly affects the activity of hepatic CYP. In this pilot study, we assess the impact of intravenous nitrate treatment on the antiplatelet effects of clopidogrel in patients with non-ST-elevation myocardial infarction (NSTEMI).MethodWe included 20 NSTEMI patients: 15 in the nitrate group and five in the control group. All patients received a 300 mg acetylsalicylic acid and a 600 mg clopidogrel loading dose. The nitrate group was administered an intravenous glyceryl trinitrate infusion at 10 µg/min for 48 h. After the drugs were initiated, blood samples were collected from patients at intervals of 30th minutes, 60th minutes, 120th minutes, fourth hour, sixth hour, and 48th hour to assess platelet function. The antiplatelet effect of clopidogrel was evaluated using the platelet reactivity unit (PRU) from the Verify-Now P2Y12 assay.ResultThe PRU values at baseline and the 30th, 60th, 120th minutes, and 48th hour were similar between the two groups (P > .05). However, PRU values at the fourth and sixth hours were significantly higher in the nitrate group than in the control group (274.1 ± 53.9 vs 162.4 ± 39.9; P = .002 and 272.0 ± 67.0 vs 185.6 ± 18.1; P = .03, respectively).ConclusionIntravenous nitrate therapy in patients with NSTEMI delayed the onset of the antiplatelet effect of orally loaded clopidogrel by at least 4 h. This point should be kept in mind in patients using clopidogrel and nitrate therapy together. (NCT06878638).

Background and aimsRenin-angiotensin-aldosterone system (RAAS) inhibition is an upstream therapy for managing atrial fibrillation (AF). Of all RAAS-inhibiting agents, only canrenone in the form of potassium canrenoate, a specific inhibitor of mineralocorticoid receptors, is administered intravenously. We evaluated the clinical efficacy of intravenous potassium canrenoate in restoring sinus rhythm in patients with paroxysmal AF episodes.MethodsThis double-center, randomized, double-blind study comprised 52 patients with AF (lasting <48 h) in stable cardiopulmonary conditions who were eligible for cardioversion. The patients were randomly assigned to receive a slow intravenous bolus of 10 ml either as a placebo (0.9% saline) or canrenone (200 mg). The primary endpoint was the return of sinus rhythm within 2 h after drug administration.ResultsOf 52 patients, 27 (51.9%) and 25 (48.1%) were treated with placebo and canrenone, respectively. The median patient age was 68 years, and 27 patients (51.9%) were men. Sinus rhythm restoration during the follow-up period occurred in 3 (11.5%) and 4 (16.0%) patients in the placebo and canrenone arms (P = .477), respectively. Adverse events were observed in 2 (7.4%) and 0 (0.0%) patients in the placebo and canrenone arms, respectively (P = .170).ConclusionsIntravenous canrenone is not effective in the sinus rhythm restoration among the patients with paroxysmal AF.ClinicalTrials.gov. NCT03536806.

Syncope refers to the transient loss of consciousness and the most common type of syncope is vasovagal syncope (VVS), usually occurring when a person is in an upright position, and/or after exposure to intense stress. The sequelae of VVS is caused by an increase in sympathetic tone and heart rate combined with an underfilled left ventricular chamber that leads to stimulation of cardiac afferent C fibers ultimately leading to bradycardia and vasodilation causing a reduction in venous return, cerebral hypoperfusion and VVS. Several treatment options have been tested including physical counter-pressure measures, electrical pacing, cardioneuroblation. Pharmacological interventions and clinical trials for VVS are summarized in this review; however, there is still limited evidence of their efficacy for reducing episodes of VVS. This review will examine studies using animal models of the vasovagal reflex arc to investigate the physiological mechanisms and neurotransmitters associated with VVS, the tilt-table test that induces VVS in patients and the potential sources of cardiac and platelet mediators that can activate cardiac afferent C fibers. This study will also consider how the previously investigated pharmacotherapies provide insight into the multiple mechanisms involved in VVS and propose new targets for the pharmacological treatment of VVS.

BackgroundLncRNAs are pivotal regulators in cardiovascular diseases. Sirt1-AS, a lncRNA, has been shown to play a role in cardiovascular diseases. This study aimed to explore the role of Sirt1-AS in cardiac hypertrophy and the underlying molecular mechanism.MethodsA mouse model of pressure-overload cardiac hypertrophy was established via transverse aortic constriction (TAC). Cardiac tissues of TAC mice and cardiomyocytes treated with angiotensin II (AngII) were examined for Sirt1-AS and Sirt1 expression levels. The effects of Sirt1-AS overexpression or knockdown on cardiomyocyte size and hypertrophic marker expression were accessed. Furthermore, the molecular interaction between Sirt1-AS and Sirt1 were investigated.ResultsSirt1-AS expression was found to be downregulated in the hearts of TAC mice and in Ang II-treated cardiomyocytes. Overexpression of Sirt1-AS attenuated cardiac hypertrophy, while its suppression exacerbated the hypertrophic response. Mechanistic studies demonstrated that Sirt1-AS directly influenced Sirt1 mRNA and protein expression levels. Moreover, the protective effects of Sirt1-AS against cardiac hypertrophy were abolished upon Sirt1 mRNA inhibition.ConclusionOur findings suggest that Sirt1-AS exerts a protective effect against cardiac hypertrophy by modulating Sirt1 expression. This research provides novel insights into the role of lncRNAs in cardiac hypertrophy and highlights Sirt1-AS as a potential therapeutic target for the treatment of cardiac hypertrophy.

BackgroundThe concomitant therapy of amiodarone with direct oral anticoagulants (DOACs) significantly increases the concentrations of DOACs and may increase the bleeding risks. Multiple real-world studies compared the concomitant therapy of amiodarone and DOACs versus the DOAC alone, but their main findings were contradictory.MethodsA meta-analysis compared the concomitant therapy of amiodarone and DOACs versus DOACs monotherapy. Database searches through May 1, 2025, were performed. The primary outcome was major bleeding. The secondary outcomes included stroke or systemic embolism, any bleeding, all-cause mortality, gastrointestinal bleeding, and intracranial bleeding.ResultsThis meta-analysis included a total of nine studies. There were no significant differences in major bleeding between the concomitant therapy of amiodarone and DOAC and DOAC monotherapy groups (OR 1.12; 95% CI 0.98, 1.27; P = .09; I² = 64%). No significant differences in any bleeding (OR 1.18; 95% CI 0.88, 1.57; P = .27; I² = 77%), gastrointestinal bleeding (OR 0.97; 95% CI 0.84, 1.11; P = .65; I² = 56%), and intracranial bleeding (OR 1.14; 95% CI 1.00, 1.30; P = .05; I² = 32%) were also found between the two groups. No significant differences in stroke or systemic embolism were found between the two groups (OR 0.86; 95% CI 0.74, 1.00; P = .05; I² = 34%).Conclusion and RelevanceThe concomitant therapy of amiodarone and DOACs did not significantly increase the bleeding risks or decrease the risk of stroke or systemic embolism compared to the DOAC monotherapy. The drug-drug interactions between amiodarone and DOACs may not be clinically significant.