Journal of Cardiovascular Translational Research最新文献

Diabetic cardiomyopathy (DCM) is a common complication of diabetes, characterized by myocardial injury, fibrosis, and heart dysfunction. The pathogenesis remains poorly understood, with limited treatment options. Recent research highlights the roles of regulated cell death (RCD) and inflammation in DCM progression. RCD types, including apoptosis, pyroptosis, ferroptosis, and necroptosis, are central to myocardial damage and are closely linked to oxidative stress and inflammation. Inflammatory pathways like NLRP3, NF-κB, and TLR4 activate cytokines (TNF-α, IL-1β, IL-6), exacerbating fibrosis and heart failure. Notably, RCD and inflammation create a feedback loop, amplifying each other and accelerating DCM. This review explores the interactions between RCD and inflammatory signaling, their contribution to myocardial injury, and potential therapeutic strategies targeting both pathways. A multi-targeted approach to DCM therapy may offer new avenues for treatment.

Inherited cardiac arrhythmias are genetic disorders that impact the heart's electrical circuitry. These disorders are caused by inherited mutations and markedly increase the mortality risk of affected individuals. Conventional treatments, such as pharmacological agents for rate and rhythm control or surgical interventions, are often not efficacious and cause long-term complications. Gene therapy has recently emerged as a feasible and potentially curative approach for treating inherited cardiac arrhythmia syndromes. Advancements in elucidating the molecular mechanisms, pinpointing essential candidate genes, and improving gene delivery have rendered gene therapy as a feasible treatment alternative. This review examines recent studies on gene therapy applications in Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, long QT syndrome, familial atrial fibrillation, and arrhythmogenic cardiomyopathy. Additionally, we analyze current advancements in viral and non-viral gene delivery methods, highlighting their therapeutic potential and related challenges.

Individuals with severe obesity (SO) are at a high risk of developing cardiovascular disease, but traditional lipid parameters are insufficient for accurately assessing the risk. This study aims to investigate the advanced characteristics of lipoproteins that may contribute to subclinical atherosclerosis in SO and the impact of bariatric surgery (BS). The study included 37 patients with SO with a one-year follow-up post-BS, and 40 control subjects. Advanced lipoprotein profiles were assessed using nuclear magnetic resonance. BS normalized proatherogenic lipoprotein alterations in SO. Small LDL and medium HDL particle numbers differed between plaque and non-plaque groups. A ratio of these particles showed an AUC of 83%, suggesting it could effectively predict subclinical atherosclerosis. Advanced NMR analysis offers more specific information on lipid profiles in SO. The small LDL-P to medium HDL-P ratio could be a valuable tool for detecting and managing subclinical atherosclerosis in this population.

Recent research shows exercise is good for heart health, emphasizing the importance of physical activity. Sedentary behavior increases the risk of cardiovascular disease, while exercise can help prevent and treat it. Additionally, physical exercise can modulate the expression of lncRNAs, influencing cardiovascular disease progression. Therefore, understanding this relationship could help identify prospective biomarkers and therapeutic targets pertaining to cardiovascular ailments. This review has underscored recent advancements concerning the potential biomarkers of lncRNAs in cardiovascular diseases, while also summarizing existing knowledge regarding dysregulated lncRNAs and their plausible molecular mechanisms. Additionally, we have contributed novel perspectives on the underlying mechanisms of lncRNAs, which hold promise as potential biomarkers and therapeutic targets for cardiovascular conditions. The knowledge imparted in this review may prove valuable in guiding the design of future investigations and furthering the understanding of lncRNAs as diagnostic, prognostic, and therapeutic biomarkers for cardiovascular diseases.

Inflammation is a key contributor to cardiovascular disease (CVD), yet existing risk models such as Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) and Pooled Cohort Equations (PCE) inadequately identify individuals at intermediate risk. We investigated whether incorporating the inflammatory chemokine CCL17 could improve cardiovascular risk prediction. In two prospective cohorts-the Shunyi Cohort (n = 706, China) and the UK Biobank (n = 36,097, UK)-baseline CCL17 levels were quantified, and major adverse cardiovascular events (MACEs) were tracked over follow-up. Elevated CCL17 levels were independently associated with increased risk of MACEs. Integrating CCL17 into existing models significantly improved discrimination and reclassification, particularly among intermediate-risk individuals (e.g., NRI: 15.1% in Shunyi; 3.0% in UK Biobank). This biomarker-based refinement enabled earlier identification of clinically significant high-risk individuals. These findings suggest that CCL17 is a promising translational biomarker that may enhance precision prevention by augmenting current cardiovascular risk assessment strategies.

Cardiac surgery with cardiopulmonary bypass (CPB) may lead to many postoperative complications. However, many complications cannot be predicted in time using the current clinical methods, or the prediction is not sufficiently accurate, resulting in a delay in treatment. Extracellular vesicles (EVs) are a group of membrane vesicles generated from various sources, including endothelial cells and platelets, upon activation or apoptosis. Here, we summarize the role of circulating EVs in predicting complications after cardiac surgery with cardiopulmonary bypass. We found that EV levels can predict acute heart failure. EV subtypes can predict acute heart failure, acute kidney injury, acute lung injury, blood transfusion, and neurological complications. The components of EVs can predict acute heart failure, acute kidney injury, acute lung injury, and neurological complications. The size distribution of EVs can predict acute lung injury. Therefore, circulating EVs can be used to predict complications after cardiac surgery with cardiopulmonary bypass.

Perivascular adipose tissue (PVAT) influences the tone of vascular function through its endocrine, paracrine, and vasocrine functions. Obesity-induced PVAT inflammation promotes vascular dysfunction by shifting its secretory profile to a proinflammatory state. The intertwined nature of PVAT and vascular dysfunction in obesity calls for a drug that can target both simultaneously for effective mitigation of cardiovascular complications. Current therapeutic strategies target either systemic inflammation or vasoregulation, while a dual-targeting approach remains unexplored. Des-aspartate-angiotensin I (DAA-I) is a circulating angiotensin peptide with anti-inflammatory and vasoregulatory properties by modulating angiotensin receptor subtype 1 (AT1R). This review investigates DAA-I as a promising therapeutic agent that can target both PVAT inflammation and endothelial dysfunction simultaneously. It summarises the documented pharmacological potential of DAA-I, its impact on vascular function, and its potential implications for future clinical applications. Understanding its dual action could open an avenue for innovative therapeutic intervention in obesity-related cardiovascular diseases.

Heart failure with preserved ejection fraction (HFpEF) is a complex multisystem syndrome with increasing prevalence in aging and metabolically compromised populations. In addition to diastolic dysfunction, HFpEF involves metabolic abnormalities, chronic inflammation, and oxidative stress across kidney, lung, liver, adipose tissue, and skeletal muscle. Interorgan crosstalk plays a key role in disease progression. Current treatments including SGLT2 inhibitors, GLP-1 receptor agonists, combined with lifestyle interventions like exercise and diet, offer potential benefits for specific subgroups, but broader efficacy remains limited. In this review, we summarized the pathophysiological characteristics of HFpEF from a multi-organ perspective, encompassing intrinsic cardiac mechanisms, cardio-renal and cardio-hepatic interactions, pulmonary and skeletal muscle abnormalities, regional adiposity, and endothelial dysfunction. Future strategies emphasizing multi-organ integration to develop individualized, mechanism-based therapies for the precision treatment and comprehensive management of HFpEF were further discussed.

Left ventricular diastolic dysfunction (LVDD), confirmed by left heart catheterization, is the gold standard for diagnosing heart failure with preserved ejection fraction (HFpEF). However, current noninvasive diagnostic tools may fail to detect early-stage LVDD in patients without prior hospitalization for heart failure, delaying timely intervention. Given its role in inflammation and cardiovascular remodeling, serum interleukin-8 (IL-8) may serve as a potential biomarker for early detection. We conducted a retrospective cohort study that included patients who underwent diagnostic left heart catheterization between March 2020 and August 2024. In the discovery cohort (n = 1,014), we assessed the associations of 12 inflammatory cytokines with catheterization-confirmed LVDD via a highly sensitive flow cytometer. IL-8, the most strongly associated cytokine, was further evaluated in a separate prospective validation cohort (n = 248). Diagnostic performance was evaluated via the area under the receiver operating characteristic curve (AUC). IL-8 levels were significantly elevated in LVDD patients without atrial fibrillation compared with controls, with a 2.26-fold median increase (P < 0.001). In the discovery cohort (n = 1,014), IL-8 was independently associated with LVDD (adjusted odds ratio for highest vs. lowest quartile: 13.2 [95% CI: 6.5-26.7]). These findings were validated in an independent cohort. Combining IL-8 with B-type natriuretic peptide (BNP) and the E/e' ratio improved diagnostic accuracy, achieving an AUC of 0.79 (95% CI: 0.74-0.85). Serum IL-8 is an independent biomarker for diagnosing catheterization-confirmed LVDD in patients without atrial fibrillation. Its combination with traditional markers enhances diagnostic performance, offering a promising tool for early identification and potential risk stratification of HFpEF. Clinically, IL-8 testing may help identify patients with unexplained dyspnea who warrant closer monitoring or earlier therapeutic intervention.