Cardiovascular Therapeutics最新文献

Heart failure (HF) and renal dysfunction often coexist and interact in many complex and bidirectional pathways, leading to detrimental effects on patient outcomes. The treatment of HF patients with renal dysfunction presents a significant clinical challenge. Interestingly, sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor (ARNI), may have beneficial effects on cardiac and renal outcomes in patients with HF with reduced ejection fraction, particularly by slowing the rate of decrease in the estimated glomerular filtration rate compared to a single angiotensin–converting enzyme inhibitor. Recently, more reports have emphasized the renal protection of sacubitril/valsartan in patients with HF. In HF patients with renal dysfunction, however, there is no strong evidence supporting the use of sacubitril/valsartan to reduce the absolute risk of hyperkalemia and worsening renal function; therefore, the administration of ARNI requires a careful balance between the benefits and risks. Furthermore, the lack of evidence-based management highlights the importance of an individualized approach based on published experience and multidisciplinary collaborations, as well as underlines the need for in-depth studies investigating the underlying mechanisms in cardiorenal interactions with a focus on treatments.

Objective: This research is aimed at unravelling the intricate relationship between transient receptor potential vanilloid 6 (TRPV6), protein kinase A (PKA), uncoupling protein 2 (UCP2), and atherosclerosis. By shedding light on the role of the TRPV6/PKA/UCP2 pathway in inhibiting inflammatory response and cell apoptosis in coronary atherosclerotic plaques, this study provides valuable insights into potential therapeutic targets for treating coronary artery disease (CAD).

Methods: We established animal and cell models of atherosclerosis. The expression of TRPV6 was measured using immunohistochemistry and immunofluorescence. Cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability and apoptosis ratio were measured using cell counting kit-8 (CCK-8) and flow cytometry. The binding relationship between TRPV6 and PKA was validated using chromatin immunoprecipitation (CHIP) and coimmunoprecipitation (CoIP). Finally, the expression of the TRPV6/PKA/UCP2 signaling pathway and apoptosis-related factors was detected using western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR).

Results: TRPV6 was significantly decreased in atherosclerosis mouse and cell model. CHIP and CoIP assays indicated that TRPV6 binds to PKA and positively regulated its expression in oxidized low-density lipoprotein (ox-LDL)–treated human umbilical vein endothelial cells (HUVECs). Overexpression of TRPV6 significantly increased cell viability and inhibited apoptosis, whereas silencing TRPV6 had the opposite effect. Additionally, the overexpression of TRPV6 remarkably declined the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). However, after silencing PKA, this effect was partially reversed, the cell viability and inflammatory response remarkably enhanced, and apoptosis significantly declined in oe-TRPV6 + si-PKA group.

Conclusions: In summary, our study demonstrated that TRPV6 inhibited apoptosis and inflammatory response in the atherosclerosis cell model through the regulation of the PKA/UCP2 pathway.

Background: The research is aimed at exploring the potential of marigold petal tea (MPT), rich in polyphenol contents, against oxidative stress and obesity in a rat model following a high-fat-sugar diet (HFSD).

Methods: The MPT was prepared through the customary method of decoction and was subjected to analysis for its polyphenol composition using reversed-phase high-performance liquid chromatography (RP-HPLC). Two specific doses of MPT, namely, 250 and 500 mg/kg body weight (BW), were chosen for the study—referred to as MPT-250 and MPT-500, respectively.

Result: The main phenolic acids and flavonoids identified in MPT, with concentrations exceeding 10 mg/100 mL of tea, included catechin, rutin, salicylic acid, gallic acid, sinapic acid, chlorogenic acid, cinnamic acid, and ellagic acid. The total phenolic (TP) and total flavonoid (TF) contents in MPT were measured to be 5.53 and 7.73 mg/g, respectively. Additionally, MPT demonstrated a 57.2% scavenging capacity with 2,2-diphenyl-1-picrylhydrazyl radical. Notably, the administration of a higher dose (MPT-500) showed a significant reduction in body mass index (BMI) and a 51.24% reduction in the rate of increase in BW compared to the HFSD group. The findings indicated that all the treatment groups, that is, orlistat treatment (OT), MPT-250, and MPT-500 groups, experienced reduced levels of serum total cholesterol (TC), triglyceride (TG), and markers of lipoproteins in contrast to the HFSD group. Moreover, MPT helped restore the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), thereby demonstrating its potential in combating oxidative stress. The MPT-500 group also displayed decreased liver and kidney weights and an improved atherogenic index when compared to the HFSD group.

Conclusion: The results clearly indicate that a high dosage of MPT showed antiobesity activity which was comparable to the same effects produced by the conventional drug orlistat.

Background: Atrial fibrillation (AF) is affected by both environmental and genetic factors. Previous genetic association studies, especially genome-wide association studies, revealed a large group of AF-associated genes. However, little is known about the functions and interactions of these genes. Moreover, established genetic variants of AF contribute modestly to AF variance, implying that numerous additional AF-associated genetic variations need to be identified. Hence, a systematic network and pathway analysis is needed.

Methods: We retrieved all AF-associated genes from genetic association studies in various databases and performed integrative analyses including pathway enrichment analysis, pathway crosstalk analysis, network analysis, and microarray meta-analysis.

Results: We collected 254 AF-associated genes from genetic association studies in various databases. Pathway enrichment analysis revealed the top biological pathways that were enriched in the AF-associated genes related to cardiac electromechanical activity. Pathway crosstalk analysis showed that numerous neuro-endocrine-immune pathways connected AF with various diseases including cancers, inflammatory diseases, and cardiovascular diseases. Furthermore, an AF-specific subnetwork was constructed with the prize-collecting Steiner forest algorithm based on the AF-associated genes, and 24 novel genes that were potentially associated with AF were inferred by the subnetwork. In the microarray meta-analysis, six of the 24 novel genes (APLP1, CREB1, CREBBP, PRMT1, IRAK1, and PLXND1) were expressed differentially in patients with AF and sinus rhythm.

Conclusions: AF is not only an isolated disease with abnormal electrophysiological activity but might also share a common genetic basis and biological process with tumors and inflammatory diseases as well as cardiovascular diseases. Moreover, the six novel genes inferred from network analysis might help detect the missing AF risk loci.

Patients with stable coronary artery disease (CAD) are at an increased risk of acute myocardial infarction (AMI), particularly among older individuals. Developing a reliable model to predict AMI occurrence in these patients holds the potential to expedite early diagnosis and intervention. This study is aimed at establishing a circulating amino acid-assisted model, incorporating amino acid profiles alongside clinical variables, to predict AMI risk. A cohort of 874 CAD patients from two independent centers was analyzed. Plasma amino acid levels were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) employing a targeted metabolomics approach. This methodology incorporated ¹³C isotope-labeled internal standards for precise quantification of 27 amino acids. Univariate logistic regression was applied to identify differentially expressed amino acids that distinguished between stable CAD and AMI patients. To assess prediction performance, receiver operating characteristic (ROC) curve and nomogram analyses were utilized. Five amino acids—lysine, methionine, tryptophan, tyrosine, and N6-trimethyllysine—emerged as potential biomarkers (p < 0.05), exhibiting significant differences in their expression levels across the two centers when comparing stable CAD with AMI patients. For AMI risk prediction, the base model, utilizing 12 clinical variables, achieved areas under the curve (AUC) of 0.7387 in the discovery phase (n = 623) and 0.8205 in the external validation set (n = 251). Notably, the integration of these five amino acids into the prediction model significantly enhanced its performance, increasing the AUC to 0.7651 in the discovery phase (Delong’s test, p = 1.43e-02) and to 0.8958 in the validation set (Delong’s test, p = 8.91e-03). In conclusion, the circulating amino acid-assisted model effectively enhances the prediction of AMI risk among CAD patients, indicating its potential clinical utility in facilitating early detection and intervention.

Background: Coronary angiography, an invasive diagnostic procedure, often induces pain and anxiety in patients. Despite the potential for alleviating discomfort, the use of stress balls as a nonpharmacological intervention during angiography remains underexplored.

Objective: This study is aimed at investigating the impact of stress ball application on pain and anxiety levels in patients undergoing angiography.

Methods: This randomized controlled trial was conducted on adult patients undergoing angiography at a Cardiovascular Surgery Clinic in Eastern Turkey between January 2023 and June 2023. A total of 120 patients were randomly assigned to receive stress ball application in addition to routine care. Data collection utilized the Numerical Rating Scale (NRS), Patient Information Form, and State-Trait Anxiety Inventory (STAI).

Results: Analysis revealed a significantly lower increase in mean NRS posttest scores among patients in the experimental group compared to the control group (p < 0.05). Additionally, the mean STAI posttest score demonstrated a significant decrease (p < 0.05) in the experimental group. A positive and significant correlation was observed between the mean NRS and STAI posttest scores among study group patients (p < 0.05), indicating a reduction in anxiety levels with decreasing pain.

Conclusion: The application of stress balls during angiography was associated with decreased anxiety and pain levels in patients. Stress ball intervention may serve as a beneficial adjunct to pharmacological treatments. This study underscores the potential of nonpharmacological interventions in enhancing patient comfort during invasive procedures.

Trial Registration: ClinicalTrials.gov Identifier: NCT06131606 (http://clinicaltrials.gov).

Detection of biomarkers was extremely important for the early diagnosis, prognosis, and therapy optimization of diseases. The purpose of this study was to investigate the differences in serum metabolites between patients with heart failure (HF) and healthy control (HC) and to diagnose HF qualitatively. In this study, serum samples from 83 patients with HF and 35 HCs were used as the research subjects for untargeted metabolomic analysis using ultraperformance liquid chromatography combined with quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) technology. Potential biomarkers were screened and validated using the orthogonal partial least squares discriminant analysis (OPLS-DA), random forest (RF), binary logistic regression (BLR), and receiver operating characteristic (ROC) analysis. The results indicated that a total of 43 metabolites were considered as differentially expressed metabolites (DEMs). Among these DEMs, glycodeoxycholate was identified as a specific biomarker of HF. A ROC curve analysis for HC versus HF discrimination showed an area under the ROC curve (AUC) of 0.9853 (95% CI: 0.9859–1.0000), a sensitivity of 95%, and a specificity of 100%. Hence, glycodeoxycholate might serve as a potential biomarker for HF. Furthermore, the amino acid metabolism was screened as the most significantly altered pathway in patients with HF. By identifying serum biomarkers and analyzing metabolic pathways, our study provided opportunities to enhance the understanding of the pathogenesis and early diagnosis of HF.

Objective: To observe the effects of cardiac rehabilitation guided by cardiopulmonary exercise testing (CPET) on cardiorespiratory reserve function, blood pressure, blood pressure variability, and lipid metabolism in patients with hypertension.

Methods: A randomized trial enrolled 67 Grade 1 hypertensive patients on antihypertensive drugs, divided into conventional (n = 35) and CPET (n = 32) groups. Antihypertensive drugs were not adjusted in both groups during the study period. Blood pressure, cardiorespiratory indicators, lipid profile, and BMI were assessed pre/post 12 weeks.

Results: Postintervention, the CPET group exhibited significantly lower blood pressure levels and improved cardiac indicators compared to the conventional group (p < 0.05). CPET group showed greater improvements in cardiorespiratory endurance indicators (p < 0.05). The cardiorespiratory endurance indicators showed significantly greater increases in the CPET group compared to the conventional group (p < 0.05). Low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and body mass index (BMI) were significantly lower in the CPET group (p < 0.05).

Conclusion: In addition to drug treatment, cardiac rehabilitation guided by CPET can effectively improve blood pressure control, reduce blood pressure variability, improve cardiorespiratory function and lipid metabolism, and increase exercise endurance in patients with Grade 1 hypertension. Its efficacy is clear and safe, with clinical value for promotion.

Background: The COVID-19 virus not only has significant pathogenicity but also influences the progression of many diseases, altering patient prognosis. Cardiovascular diseases, particularly aortic aneurysms, are among the most life-threatening conditions.

Main Idea: COVID-19 infection is reported to accelerate the progression of abdominal aortic aneurysms (AAAs) and increase the risk of rupture; however, a comprehensive understanding of the underlying mechanisms remains elusive. This article primarily reviews the relevant foundational research, focusing on disruptions in the renin-angiotensin-aldosterone system (RAAS), immune system activation, and coagulation disorders. Furthermore, we summarize related clinical research, including the epidemiology of aortic aneurysms during the pandemic and specific case studies.

Conclusion: COVID-19 infection can influence the onset and progression of aortic aneurysms by affecting the RAAS, triggering inflammation and immune dysregulation in the arterial wall, and inducing a hypercoagulation state. It is crucial to comprehensively understand the impact of pandemic viral infections on aortic diseases at the foundational and clinical levels, thereby identifying potential preventative or therapeutic approaches and preparing for potential future outbreaks.

Given the heightened risk of diabetes-related cardiovascular events associated with inactivity, this study investigates the molecular mechanisms of vascular damage in streptozotocin (STZ)-induced diabetic rats. The aim is to elucidate the impact of different exercises (interval and continuous training) and metformin on biochemical parameters, aortic injury, oxidative stress, and inflammation to provide insights into potential therapeutic interventions for diabetes-associated vascular complications. Male Wistar rats were administered a single dose of STZ (60 mg/kg) to induce diabetes. Diabetic rats underwent either interval training or continuous training (40 min/day, 5 days/week, 6 weeks), received metformin (300 mg/kg), or a combination of metformin and exercise. After 6 weeks, biochemical parameters in serum and oxidative stress markers and mRNA expression of endothelial nitric oxide synthase (eNOS), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and intercellular adhesion molecule-1 (ICAM-1) in aorta tissue were assessed. Serum levels of fasting blood sugar (FBS), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), TG/HDL, TC/HDL, and LDL/HDL ratios were significantly reduced in all treatment groups compared to the diabetes group. Both types of exercises, metformin, and exercise+metformin combinations, significantly reduced oxidative stress by decreasing malondialdehyde (MDA) and enhancing the antioxidant status in the aortic tissue compared to the diabetic group. In addition, in exercise groups, metformin, and combination groups, the expression of eNOS was significantly elevated, while LOX-1 and ICAM-1 expression significantly decreased compared to the diabetic group. In most cases, the combination of exercise and metformin (especially interval training) was more effective than exercise alone. It seems that exercise along with taking metformin can be considered as a therapeutic method by improving hyperglycemia and hyperlipidemia and reducing oxidative stress and vascular inflammatory responses, leading to ameliorating biomarkers function related to endothelial damage in experimental diabetes conditions.