Hemodiafiltration: a synergy yet to be convincing / Hemodiafiltração: uma sinergia ainda não convincente

ABSTRACT The desperate attempt to improve mortality, morbidity, quality of life and patient-reported outcomes in patients on hemodialysis has led to multiple attempts to improve the different modes, frequencies, and durations of dialysis sessions in the last few decades. Nothing has been more appealing than the combination of diffusion and convection in the form of hemodiafiltration. Despite the concrete evidence of better clearance of middle weight molecules and better hemodynamic stability, tangible evidence to support the universal adoption is still at a distance. Survival benefits seen in selected groups who are likely to tolerate hemodiafiltration with better vascular access and with lower comorbid burden, need to be extended to real life dialysis patients who are older than the population studied and have significantly higher comorbid burden. Technical demands of initiation hemodiafiltration, the associated costs, and the incremental benefits targeted, along with patient-reported outcomes, need to be explored further before recommending hemodiafiltration as the mode of choice.

RESUMO A tentativa desesperada de melhorar a mortalidade, morbidade, qualidade de vida e desfechos relatados pelos pacientes em indivíduos em hemodiálise levou a diversas tentativas de aprimorar os diferentes modos, frequências e durações das sessões de diálise nas últimas décadas. Nada foi mais atrativo do que a combinação de difusão e convecção na forma de hemodiafiltração. Apesar das evidências concretas de melhor depuração de moléculas de peso médio e melhor estabilidade hemodinâmica, evidências tangíveis para apoiar a adoção universal ainda estão distantes. Os benefícios de sobrevida observados em grupos selecionados que provavelmente toleram a hemodiafiltração com melhor acesso vascular e com menor carga de comorbidades precisam ser estendidos aos pacientes reais em diálise, que são mais velhos do que a população estudada e apresentam uma carga de comorbidades significativamente maior. As exigências técnicas do início da hemodiafiltração, os custos associados e os benefícios incrementais almejados, juntamente com os desfechos relatados pelos pacientes, precisam ser melhor explorados antes de se recomendar a hemodiafiltração como o modo de escolha.

Relationship between remnant cholesterol and short-term prognosis in acute ischemic stroke patients.

OBJECTIVE: Several studies have illustrated that elevated RC levels are related to a heightened risk of acute ischemic stroke (AIS). Our research aimed to explore the correlation between RC levels and poor prognosis after a 90-day interval in AIS patients. METHODS: A total of 287 individuals were enrolled in the study, the primary outcome was defined as poor prognosis. RC was derived by the exclusion of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from total cholesterol (TC). RESULTS: Following the screening process, 253 AIS patients were included in the study, presenting a median age of 66[57, 75] years. Upon stratifying RC levels into quartiles, those in the top quartile faced a greater likelihood of diabetes diagnosis (42.86%, p = .014) and experienced a higher rate of unfavorable outcomes after 90 days (36.51%, p = .001). After accounting for confounding factors, the correlation between the fourth quartile of RC levels and the amplified likelihood of poor prognosis remained significant (odds ratio (OR) 8.471, 95% confidence interval (CI) (1.841, 38.985); p = .006). Analysis of subgroups unveiled a notable correlation between higher RC levels and poor 90-day prognosis, particularly in individuals with elevated NIHSS scores (p = .044). A progressively increasing 90-day risk of poor prognosis after an RC greater than 0.38 mmol/L was visualized by restricted cubic spline plots (p-overall = .011). CONCLUSIONS: Including RC as a contributing element may refine the prediction of poor 90-day prognosis for AIS patients. Integrating RC with traditional risk factors can potentially enhance the predictive value for cerebrovascular disease.

The association between lower extremity function and cardiovascular diseases risk in older Chinese adults: Longitudinal evidence from a nationwide cohort.

BACKGROUND: Older adults in China are at a high risk of cardiovascular diseases (CVD), and impaired lower extremity function (LEF) is commonly observed in this demographic. This study aimed at assessing the association between LEF and CVD, thus providing valuable insights for clinical practice and public health policies. METHODS: A sample of 4,636 individuals was included from the China Health and Retirement Longitudinal Study (CHARLS) dataset. Logistic regression and cox proportional hazard regression model was utilized to study the association between LEF and CVD incidence. Cross-lagged panel models were utilized to investigate the potential causal association between LEF and CVD over time. RESULTS: Poor LEF was significantly associated with a higher risk of CVD in the total population [OR (95 % CI): 1.62 (1.27-2.05), P < 0.001]. Individuals with poor LEF demonstrated an increased risk of developing CVD [HR (95 % CI): 1.11 (1.02-1.23), P < 0.05], particularly stroke, compared to those with good LEF. And those with poor LEF had higher risks for heart disease [1.21 (1.00-1.45), P < 0.05] and stroke [1.98 (1.47-2.67), P < 0.001]. CONCLUSION: The results suggest the potential usefulness of the Short Physical Performance Battery (SPPB) for classifying stroke risk in older Chinese adults, which also suggested that preventing and/or improving LEF may be beneficial for reducing stroke incidence and promoting healthy aging for older adults.

The Art of Healing Hearts: Mastering Advanced RNA Therapeutic Techniques to Shape the Evolution of Cardiovascular Medicine in Biomedical Science.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are associated with increasing financial health burden that requires research into novel therapeutic approaches. Since the early 2000s, the availability of next-generation sequencing techniques such as microRNAs, circular RNAs, and long non-coding RNAs have been proven as potential therapeutic targets for treating various CVDs. Therapeutics based on RNAs have become a viable option for addressing the intricate molecular pathways that underlie the pathophysiology of CVDs. We provide an in-depth analysis of the state of RNA therapies in the context of CVDs, emphasizing various approaches that target the various stages of the basic dogma of molecular biology to effect temporary or long-term changes. In this review, we summarize recent methodologies used to screen for novel coding and non-coding RNA candidates with diagnostic and treatment possibilities in cardiovascular diseases. These methods include single-cell sequencing techniques, functional RNA screening, and next-generation sequencing.Lastly, we highlighted the potential of using oligonucleotide-based chemical products such as modified RNA and RNA mimics/inhibitors for the treatment of CVDs. Moreover, there will be an increasing number of potential RNA diagnostic and therapeutic for CVDs that will progress to expand for years to come.

Risk of cardiovascular and respiratory diseases attributed to satellite-based PM2.5 over 2017-2022 in Sanandaj, an area of Iran.

The risk of cardiovascular and respiratory diseases attributed to satellite-based PM2.5 has been less investigated. In this study, the attributable risk was estimated in an area of Iran. The predicted air PM2.5 using satellite data and a two-stage regression model was used as the predictor of the diseases. The dose-response linkage between the bias-corrected predictor employing a strong statistical approach and the outcomes was evaluated using the distributed lag nonlinear model. We considered two distinct scenarios of PM2.5 for the risk estimation. Alongside the risk, the attributable risk and number were estimated for different levels of PM2.5 by age and gender categories. The cumulative influence of PM2.5 particles on respiratory illnesses was statistically significant at 13-16 µg/m3 relative to the reference value (median), mostly apparent in the middle delays. The cumulative relative risk of 90th and 95th percentiles were 2.03 (CI 95%: 1.28, 3.19) and 2.25 (CI 95%: 1.28, 3.96), respectively. Nearly 600 cases of the diseases were attributable to the non-optimum values of the pollutant during 2017-2022, of which more than 400 cases were attributed to high values range. The predictor's influence on cardiovascular illnesses was along with uncertainty, indicating that additional research into their relationship is needed. The bias-corrected PM2.5 played an essential role in the prediction of respiratory illnesses, and it may likely be employed as a trigger for a preventative strategy.

Endothelial Dysfunction as a Key Link between Cardiovascular Disease and Frailty: A Systematic Review.

Background: Frailty is increasingly recognized as a significant health concern, particularly due to its association with cardiovascular pathologies. This study aims to examine how vascular endothelial dysfunction, a known premorbid stage in the pathophysiology of cardiovascular diseases, contributes to the link between cardiovascular illness and frailty. Methods: The inclusion criteria allowed us to focus on original clinical research articles published in English between January 2014 and January 2024, which reported quantitative assessments of the relationship between frailty and vascular endothelial dysfunction. Excluded from the study were systematic literature reviews, meta-analyses, editorials, conference articles, theses, methodological articles, and studies using animal or cell culture models. Searches were conducted of electronic databases, including Scopus, ScienceDirect, and Medline, up to 22 January 2024. The risk of bias was assessed using the Joanna Briggs Institute's critical appraisal tools. The methods used to present and synthesize the results involved data extraction and categorization based on biomolecular and clinical findings of endothelial dysfunction. Results: Following the application of the inclusion and exclusion criteria, a total of 29 studies were identified. Vascular endothelial dysfunction was associated with increased frailty phenotypes, and we also identified SGLT-2 inhibitors' potential role as an anti-fragility treatment that affects endothelial dysfunction. This study found that the physical and biomolecular markers of endothelial dysfunction are associated with frailty measures and have predictive value for incident frailty. Furthermore, some studies have shown inflammation to have an impact on endothelial dysfunction and frailty, and an innovative age-related chronic inflammation measure has been proven to predict frailty scores. Conclusions: The current evidence suggests an association between endothelial dysfunction and frailty, highlighting the need for further research to elucidate the underlying mechanisms.

Conceptually Funded Usability Evaluation of an Application for Leveraging Descriptive Data Analysis Models for Cardiovascular Research.

The focus of this study, and the subject of this article, resides in the conceptually funded usability evaluation of an application of descriptive models to a specific dataset obtained from the East Slovak Institute of Heart and Vascular Diseases targeting cardiovascular patients. Delving into the current state-of-the-art practices, we examine the extent of cardiovascular diseases, descriptive data analysis models, and their practical applications. Most importantly, our inquiry focuses on exploration of usability, encompassing its application and evaluation methodologies, including Van Welie's layered model of usability and its inherent advantages and limitations. The primary objective of our research was to conceptualize, develop, and validate the usability of an application tailored to supporting cardiologists' research through descriptive modeling. Using the R programming language, we engineered a Shiny dashboard application named DESSFOCA (Decision Support System For Cardiologists) that is structured around three core functionalities: discovering association rules, applying clustering methods, and identifying association rules within predefined clusters. To assess the usability of DESSFOCA, we employed the System Usability Scale (SUS) and conducted a comprehensive evaluation. Additionally, we proposed an extension to Van Welie's layered model of usability, incorporating several crucial aspects deemed essential. Subsequently, we rigorously evaluated the proposed extension within the DESSFOCA application with respect to the extended usability model, drawing insightful conclusions from our findings.

A Multi-Stage Approach for Cardiovascular Risk Assessment from Retinal Images Using an Amalgamation of Deep Learning and Computer Vision Techniques.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. Early detection and effective risk assessment are crucial for implementing preventive measures and improving patient outcomes for CVDs. This work presents a novel approach to CVD risk assessment using fundus images, leveraging the inherent connection between retinal microvascular changes and systemic vascular health. This study aims to develop a predictive model for the early detection of CVDs by evaluating retinal vascular parameters. This methodology integrates both handcrafted features derived through mathematical computation and retinal vascular patterns extracted by artificial intelligence (AI) models. By combining these approaches, we seek to enhance the accuracy and reliability of CVD risk prediction in individuals. The methodology integrates state-of-the-art computer vision algorithms and AI techniques in a multi-stage architecture to extract relevant features from retinal fundus images. These features encompass a range of vascular parameters, including vessel caliber, tortuosity, and branching patterns. Additionally, a deep learning (DL)-based binary classification model is incorporated to enhance predictive accuracy. A dataset comprising fundus images and comprehensive metadata from the clinical trials conducted is utilized for training and validation. The proposed approach demonstrates promising results in the early prediction of CVD risk factors. The interpretability of the approach is enhanced through visualization techniques that highlight the regions of interest within the fundus images that are contributing to the risk predictions. Furthermore, the validation conducted in the clinical trials and the performance analysis of the proposed approach shows the potential to provide early and accurate predictions. The proposed system not only aids in risk stratification but also serves as a valuable tool for identifying vascular abnormalities that may precede overt cardiovascular events. The approach has achieved an accuracy of 85% and the findings of this study underscore the feasibility and efficacy of leveraging fundus images for cardiovascular risk assessment. As a non-invasive and cost-effective modality, fundus image analysis presents a scalable solution for population-wide screening programs. This research contributes to the evolving landscape of precision medicine by providing an innovative tool for proactive cardiovascular health management. Future work will focus on refining the solution's robustness, exploring additional risk factors, and validating its performance in additional and diverse clinical settings.

Apolipoprotein B Secretion Assay from Primary Hepatocytes.

Apolipoprotein B (APOB) is the primary structural protein of atherogenic lipoproteins, which drive atherogenesis and thereby lead to deadly cardiovascular diseases (CVDs). Plasma levels of APOB-containing lipoproteins are tightly modulated by LDL receptor-mediated endocytic trafficking and cargo receptor-initiated exocytic route; the latter is much less well understood. This protocol aims to present an uncomplicated yet effective method for detecting APOB/lipoprotein secretion. We perform primary mouse hepatocyte isolation and culture coupled with well-established techniques such as immunoblotting for highly sensitive, specific, and semi-quantitative analysis of the lipoprotein secretion process. Its inherent simplicity facilitates ease of operation, rendering it a valuable tool widely utilized to explore the intricate landscape of cellular lipid metabolism and unravel the mechanistic complexities underlying lipoprotein-related diseases. Key features • A pipeline for the isolation and subsequent culture of mouse primary hepatocytes. • A procedure for tracking the secretion of APOB-containing lipoproteins. • A rapid and sensitive assay for detecting the APOB level based on immunoblotting.

Factors Associated With Mortality During the First Year Post Infarction: Survival Analysis of Patients With Acute Myocardial Infarction in Colombia.

INTRODUCTION: Cardiovascular diseases account for over 80% of global deaths. Risk factors and social determinants influence mortality in patients post acute myocardial infarction (AMI). OBJECTIVE: To evaluate factors associated with post-AMI mortality during the one-year follow-up. MATERIALS AND METHODS: The study is a prospective cohort study of adults aged 18 years and older with type 1 AMI conducted between October 2021 and January 2024. Intrahospital and outpatient information was collected. Statistical analyses included the Kaplan-Meier survival curve and Cox regression analysis. Proportional hazards and model predictive capacity were evaluated. RESULTS: A total of 1873 patients were included, with a 9.4% mortality rate in the first year. At one year, the estimated survival probability was 88.61% (95% CI: 86.82-90.18). Cox analysis identified several factors associated with mortality, highlighting age (HR = 1.04, 95% CI: 1.02-1.06, p = 0.001), diabetes (HR = 1.77, 95% CI: 1.09-2.87, p = 0.020), renal insufficiency (HR = 2.25, 95% CI: 1.32-3.84, p = 0.003), and type of intervention. The model evaluation showed strong predictive capacity. CONCLUSIONS: It is essential to emphasize the importance of comprehensive management in AMI patients with risk factors such as diabetes and chronic kidney disease, as they are significant predictors of mortality during the first year post infarction.

A review regarding the article 'Electrocardiographic abnormalities in patients with metabolic dysfunction-associated Steatotic liver disease: A systematic review and meta-analysis.'

Metabolic-dysfunction-associated Steatotic liver disease (MASLD) is a high-risk condition for both liver fibrosis and cardiovascular disease (CVD). Therefore, therapeutic strategies to prevent both liver fibrosis and atherosclerotic CVD are required for the treatment of MASLD. Metabolic dysfunction-associated steatohepatitis (MASH) is the more severe form of MASLD, is defined histologically by the presence of lobular inflammation and hepatocyte ballooning and is associated with a greater risk of fibrosis progression. While CVD is the leading cause of mortality in patients with MASLD, those with more severe liver fibrosis are at increased risk of liver-related mortality, with the risk increasing exponentially with fibrosis stage. MASH has been found in 63% of patients with MASLD undergoing liver biopsy in an Asian multi-center cohort. Multiple complex pathways are involved in the association between MASLD and CVD. The visceral accumulation of fat around the liver and other organs, including the pericardium, leads to the release of fat-derived metabolites with the activation of several inflammatory pathways Cardiac rhythm abnormalities are prevalent in MASLD, such as prolongation of the QT interval, ventricular arrhythmias, and atrial fibrillation. Therapeutic interventions that improve cardiometabolic risk factors may be beneficial for an improvement in MASLD. The effects of such therapeutic interventions on lipid, lipoprotein and apoprotein accumulation in the liver and on hepatic steatosis and fibrosis still remain unelucidated. Which lipid factor is crucial for developing MASLD also remains largely unknown.

The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives.

The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Thyroid cancer and cardiovascular diseases: a Mendelian randomization study.

Background: Multiple observational studies have shown associations between thyroid cancer (TC) and cardiovascular diseases (CVDs). However, the results were inconsistent, and the potential causal genetic relationship remains unclear. Methods: The genetic instruments of TC and CVDs were derived from data obtained through genome-wide association studies (GWAS). We performed the two-sample Mendelian randomization(MR) methods to investigate the causality of TC on CVDs. Summary-level statistics for CVDs, including heart failure (HF), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), ischemic stroke (IS) and venous thromboembolism (VTE). The primary method employed in this MR analysis was the Inverse Variance Weighted (IVW) approach, and four additional algorithms were used: MR-Egger, weighted median, simple mode, and weighted mode. Additionally, we assessed the reliability of the causal relationship through pleiotropy, heterogeneity and leave-one-out sensitivity analysis. Results: In this MR analysis, we only detected causality of genetically predicted TC on HF (IVW method, odds ratio (OR) = 1.00134, 95% confidence interval (CI): 1.00023-1.00244, p = 0.017). However, There were no causal associations of TC with CAD, MI, AF, IS, and VTE. Conclusion: Our results confirmed the causal association between TC and HF. It is crucial to closely monitor the incidence of HF in TC patients and give comprehensive clinical intervention based on conventional treatment.

Cardiovascular events after exacerbations of chronic obstructive pulmonary disease: Results from the EXAcerbations of COPD and their OutcomeS in CardioVascular diseases study in Italy.

INTRODUCTION: Exacerbations of chronic obstructive pulmonary disease (COPD) can increase the risk of severe cardiovascular events. OBJECTIVE: Assess the crude incidence rates (IR) of cardiovascular events and the impact of exacerbations on the risk of cardiovascular events within different time periods following an exacerbation. METHODS: COPD patients aged ≥45 years between 01/01/2015 and 12/31/2018 were identified from the Fondazione Ricerca e Salute administrative database. IRs of severe non-fatal and fatal cardiovascular events were obtained for post-exacerbation time periods (1-7, 8-14, 15-30, 31-180, 181-365 days). Time-dependent Cox proportional hazard models compared cardiovascular risks between periods with and without exacerbations. RESULTS: Of 216,864 COPD patients, >55 % were male, mean age was 74 years, frequent comorbidities were cardiovascular, metabolic and psychiatric. During an average 34-month follow-up, 69,620 (32 %) patients had ≥1 exacerbation and 46,214 (21 %) experienced ≥1 cardiovascular event. During follow-up, 55,470 patients died; 4,661 were in-hospital cardiovascular-related deaths. Among 10,269 patients experiencing cardiovascular events within 365 days post-exacerbation, the IR was 15.8 per 100 person-years (95 %CI 15.5-16.1). Estimated hazard ratios (HR) for the cardiovascular event risk associated with periods post-exacerbation were highest within 7 days (HR: 34.3, 95 %CI: 33.1-35.6), especially for heart failure (HR 50.6; 95 %CI 48.6-52.7) and remained elevated throughout 365 days (HR 1.1, 95 %CI 1.02-1.13). CONCLUSIONS: COPD patients in Italy are at high risk of severe cardiovascular events following exacerbations, suggesting the need to prevent exacerbations and possible subsequent cardiovascular events through early interventions and treatment optimization.

Label free quantitative proteomic profiling of serum samples of intellectually disabled young patients revealed dysregulation of complement coagulation and cholesterol cascade systems.

Intellectual disability is a heterogeneous disorder, diagnosed using intelligence quotient (IQ) score criteria. Currently, no specific clinical test is available to diagnose the disease and its subgroups due to inadequate understanding of the pathophysiology. Therefore, current study was designed to explore the molecular mechanisms involved in disease perturbation, and to identify potential biomarkers for disease diagnosis and prognosis. A total of 250 participants were enrolled in this study, including 200 intellectually disabled (ID) subjects from the subgroups (mild, moderate, and severe) with age and gender matched healthy controls (n = 50). Initially, IQ testing score and biochemical profile of each subject was generated, followed by label-free quantitative proteomics of subgroups of IQ and healthy control group through nano-LC/MS- mass spectrometry. A total of 310 proteins were identified, among them198 proteins were common among all groups. Statistical analysis (ANOVA) of the subgroups of ID showed 142 differentially expressed proteins, in comparison to healthy control group. From these, 120 proteins were found to be common among all subgroups. The remaining 22 proteins were categorized as exclusive proteins found only in disease subgroups. Furthermore, the hierarchical cluster analysis (HCL) of common significant proteins was also performed, followed by PANTHER protein classification and GO functional enrichment analysis. Results provides that the datasets of differentially expressed proteins, belong to the categories of immune / defense proteins, transfer carrier proteins, apolipoproteins, complement proteins, protease inhibitors, hemoglobin proteins etc., they are known to involvein immune system, and complement and coagulation pathway cascade and cholesterol metabolism pathway. Exclusively expressed 22 proteins were found to be disease stage specific and strong PPI network specifically those that have significant role in platelets activation and degranulation, such as Filamin A (FLNA). Furthermore, to validate the mass spectrometric findings, four highly significant proteins (APOA4, SAP, FLNA, and SERPING) were quantified by ELISA in all the study subjects. AUROC analysis showed a significant association of APOA4 (0.830), FLNA (0.958), SAP (0.754) and SERPING (0.600) with the disease. Apolipoprotein A4 (APOA4) has a significant role in cholesterol transport, and in modulation of glucose and lipid metabolism in the CNS. Similarly, FLNA has a crucial role in the nervous system, especially in the functioning of synaptic network. Therefore, both APOA4, and FLNA proteins represent good potential for candidate biomarkers for the diagnosis and prognosis of the intellectual disability. Overall, serum proteome of ID patients provides valuable information of proteins/pathways that are altered during ID progression.

Sleep deprivation reduces the baroreflex sensitivity through elevated angiotensin (Ang) II subtype 1 receptor expression in the nucleus tractus solitarii.

Introduction: Sleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation. Methods: Rats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype 1 receptors (AT1R) in the NTS of rats were assessed. Results: Compared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1-7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation. Discussion: In conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation.

High-density lipoprotein mimetic nano-therapeutics targeting monocytes and macrophages for improved cardiovascular care: a comprehensive review.

The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.

Multifaceted role of dynamin-related protein 1 in cardiovascular disease: From mitochondrial fission to therapeutic interventions.

Mitochondria are central to cellular energy production and metabolic regulation, particularly in cardiomyocytes. These organelles constantly undergo cycles of fusion and fission, orchestrated by key proteins like Dynamin-related Protein 1 (Drp-1). This review focuses on the intricate roles of Drp-1 in regulating mitochondrial dynamics, its implications in cardiovascular health, and particularly in myocardial infarction. Drp-1 is not merely a mediator of mitochondrial fission; it also plays pivotal roles in autophagy, mitophagy, apoptosis, and necrosis in cardiac cells. This multifaceted functionality is often modulated through various post-translational alterations, and Drp-1's interaction with intracellular calcium (Ca2 + ) adds another layer of complexity. We also explore the pathological consequences of Drp-1 dysregulation, including increased reactive oxygen species (ROS) production and endothelial dysfunction. Furthermore, this review delves into the potential therapeutic interventions targeting Drp-1 to modulate mitochondrial dynamics and improve cardiovascular outcomes. We highlight recent findings on the interaction between Drp-1 and sirtuin-3 and suggest that understanding this interaction may open new avenues for therapeutically modulating endothelial cells, fibroblasts, and cardiomyocytes. As the cardiovascular system increasingly becomes the focal point of aging and chronic disease research, understanding the nuances of Drp-1's functionality can lead to innovative therapeutic approaches.