Ma S, Wu D, Hu Y
… +6 more, Wang J, Zhang K, Liu S, Zhu Y, Yu T, Wu Y
J Cardiovasc Transl Res
· 2025 Dec · PMID 41454180
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Coronary artery calcification (CAC), a key atherosclerotic pathology, has shifted from a passive degenerative marker to an actively regulated process involving osteogenic transdifferentiation, inflammation, and cellular...Coronary artery calcification (CAC), a key atherosclerotic pathology, has shifted from a passive degenerative marker to an actively regulated process involving osteogenic transdifferentiation, inflammation, and cellular diversity. This review summarizes 30 years of research, integrating pathological mechanisms, technological advances, and clinical evidence for CAC management. Single-cell sequencing identifies distinct intimal (atherosclerosis-linked) and medial (CKD/diabetes-related) subtypes driven by pathways like BMP2/Smad and OPG/RANKL. Innovations include intravascular lithotripsy (IVL, ≥ 98% success in severe calcification) and AI improving imaging accuracy (99.2% segmentation). Challenges remain: statins' dual effects on calcification, subtype diagnostic gaps, and limited access to advanced tools (IVL unavailable in > 70% of resource-limited facilities). The synthesis highlights needs for multi-omics precision therapy, AI-based risk stratification, and cost-effective solutions to shift from reactive treatment to proactive vascular health optimization, addressing the rising burden of calcific cardiovascular disease in aging populations.
Han B, Zhu Z, Wang Y
… +4 more, Zhao N, Chen J, Zhou S, Zhang Z
J Cardiovasc Transl Res
· 2025 Oct · PMID 41166052
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Cardiac fibrosis remains a major clinical challenge with limited therapeutic options, and the role of PFKFB3 in its pathogenesis remains unclear. Single-cell RNA sequencing analysis was applied and the results demonstrat...Cardiac fibrosis remains a major clinical challenge with limited therapeutic options, and the role of PFKFB3 in its pathogenesis remains unclear. Single-cell RNA sequencing analysis was applied and the results demonstrated that glycolysis was most prominently enhanced in activated cardiac myofibroblasts (myoCFs) in cardiomyopathy. Western blot analysis revealed that PFKFB3 expression was significantly increased in fibrotic hearts and TGF-β1-stimulated myoCFs. Genetic (Pfkfb3) and pharmacological (3PO) inhibition of PFKFB3 attenuated myoCF activation, proliferation, and migration, while also reducing cardiac fibrosis in isoproterenol- and coronary ligation- induced mouse models. Mechanistically, TGF-β1 upregulated PFKFB3 in a HIF-1α-dependent manner, and extracellular PFKFB3 further promoted fibroblast activation and inflammatory responses. Clinically, elevated plasma PFKFB3 levels, as measured by ELISA, were significantly associated with fibrosis severity in patients with cardiomyopathy. These findings reveal for the first time that PFKFB3 drives cardiac fibrosis dually through intracellular glycolytic regulation and extracellular signaling, highlighting its translational potential.
Deiman FE, de Graaf MM, Sillje HHW
… +3 more, Grote Beverborg N, Bomer N, van der Meer P
J Cardiovasc Transl Res
· 2025 Dec · PMID 41166051
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RNA-based therapeutics, such as small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs) and messenger RNAs (mRNAs) are promising therapeutics that offer new avenues for targeting molecular pathways underlying...RNA-based therapeutics, such as small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs) and messenger RNAs (mRNAs) are promising therapeutics that offer new avenues for targeting molecular pathways underlying heart failure (HF) pathogenesis. This review provides an overview of RNA therapeutics, detailing their mechanisms and potential applications in the treatment of HF. Key pathological processes in HF, including dysregulated calcium handling, myocardial fibrosis, oxidative stress, inflammation and aberrant signalling, are explored to identify how RNA-based therapeutics can be utilized to address these mechanisms. Preclinical studies demonstrating the potential of RNA therapeutics to modulate these pathways are discussed. In addition, the review identifies novel therapeutic targets of HF that may allow more precise and effective interventions, potentially reversing disease progression in HF. In this way, the potential of RNA therapeutics as a next-generation treatment strategy for HF are highlighted, offering hope for more targeted and personalized approaches for HF.
J Cardiovasc Transl Res
· 2025 Dec · PMID 41166050
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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. Conven...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.
Carmona-Maurici J, Eskubi-Turró I, Viñas A
… +7 more, Ricart-Jané D, López-Tejero MD, Amigó N, Bermúdez M, Baena-Fustegueras JA, Peinado-Onsurbe J, Pardina E
J Cardiovasc Transl Res
· 2025 Dec · PMID 41160327
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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 advanc...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.
J Cardiovasc Transl Res
· 2025 Dec · PMID 41160326
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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 secre...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.
Lu Y, Cui J, Cheng X
… +5 more, Li J, Zhang L, Tian J, Yang A, Yi L
J Cardiovasc Transl Res
· 2025 Dec · PMID 41125827
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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...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.
Ma Z, Yang Z, Ji X
… +5 more, Shi M, Li L, Zhao Q, Zhen Y, Liu C
J Cardiovasc Transl Res
· 2025 Dec · PMID 41118041
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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...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.
J Cardiovasc Transl Res
· 2025 Dec · PMID 41109933
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Cardiogenic shock (CS) following myocardial infarction remains highly fatal. The prognostic value of dynamic metabolic markers-particularly glucose and cortisol-remains incompletely understood. In this prospective cohort...Cardiogenic shock (CS) following myocardial infarction remains highly fatal. The prognostic value of dynamic metabolic markers-particularly glucose and cortisol-remains incompletely understood. In this prospective cohort study, 41 patients with infarction-related CS underwent serial blood sampling over 96 h. Plasma glucose and serum cortisol levels were measured repeatedly. Primary endpoint was in-hospital mortality. Admission glucose levels stratified as < 10, 10-15, and > 15 mmol/L were associated with rising mortality (36.4%, 43.8%, 50.0%; p = 0.47). Mortality was higher in patients without known diabetes. Early glucose normalization (≤ 6 h) correlated with improved survival (25% vs. 45%; p < 0.05). Cortisol levels were markedly elevated on admission. Survivors showed rapid decline; non-survivors had persistently high levels. Cumulative cortisol exposure (AUC₀-₉₆) was significantly lower in survivors (p = 0.016). Serial metabolic profiling identified early and sustained hyperglycaemia and hypercortisolaemia as independent predictors of mortality in infarction-related CS and potential targets for intervention.
Ye X, Hu J, Cao S
… +5 more, Xu X, Jing Y, Xue Z, Lu C, Yin H
J Cardiovasc Transl Res
· 2025 Oct · PMID 41107572
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This study evaluated the effects of irreversible electroporation (IRE), a non-thermal ablation method, on carotid atherosclerotic plaques induced by high-fat feeding combined with balloon dilation in 30 rabbits. Carotid...This study evaluated the effects of irreversible electroporation (IRE), a non-thermal ablation method, on carotid atherosclerotic plaques induced by high-fat feeding combined with balloon dilation in 30 rabbits. Carotid plaques were subjected to IRE ablation (1000 V/cm alone, 2000 V/cm alone, or 1000 V/cm with rapamycin). There were no acute vascular changes post-ablation; however, IRE induced apoptosis and polarity of cells. At 7-30 days post-ablation, there was a significant decrease in lipid density within the plaque, with replacement by multilayered anterograde smooth muscle cells. Remodeling led to residual plaque becoming sandwiched between the new and original smooth muscle layers and to vessel wall thickening but with improved elasticity. Addition of rapamycin delayed remodeling. IRE reduced lipid deposition, triggered structural vascular reorganization, and improved elasticity, suggesting a potential therapeutic role in atherosclerosis. The tissue selectivity of this technique and non-thermal mechanism may offer advantages over conventional treatments.
Wang Z, Ren X, Lu Y
… +6 more, Yang J, Wu J, Zhang Y, Zhang Y, Tian Z, Zhang S
J Cardiovasc Transl Res
· 2025 Dec · PMID 41102544
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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...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.
J Cardiovasc Transl Res
· 2025 Dec · PMID 41100032
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The aim of this study was to evaluate the relationship between N,N,N trimethyl-L-alanyl-L-proline betaine (TMAP) levels and myocardial infarction (MI). Causal relationship was estimated based on TMAP levels and MI data f...The aim of this study was to evaluate the relationship between N,N,N trimethyl-L-alanyl-L-proline betaine (TMAP) levels and myocardial infarction (MI). Causal relationship was estimated based on TMAP levels and MI data from genome-wide association studies (GWAS). The main analysis method of bidirectional two-sample Mendelian randomization (TSMR) was inverse variance weighting (IVW), with four other supplementary methods used. The IVW method yielded results indicating a negative correlation between TMAP levels and MI (IVW, odds ratio [OR] = 0.976, 95% confidence interval [CI]: 0.960-0.992, P = 0.004). In contrast, the inverse analysis did not provide evidence that MI affects TMAP levels (P > 0.05). This study provided evidence for the causal effect of TMAP levels on MI. It was not the case in the opposite situation. It is plausible that TMAP may serve as a protective factor in MI.
O'Donnell C, Mikhailov A, Yoo S
… +2 more, Ghosh A, Arora R
J Cardiovasc Transl Res
· 2025 Dec · PMID 41085934
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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, yet current therapies-including drugs and catheter ablation-remain suboptimal. Gene therapy offers a promising way to modulate AF's molecular driv...Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, yet current therapies-including drugs and catheter ablation-remain suboptimal. Gene therapy offers a promising way to modulate AF's molecular drivers. This review summarizes recent preclinical studies using viral and non-viral vectors, atrial-specific delivery strategies, and key targets such as ion channels, fibrosis, and oxidative stress. Despite promising results, no AF gene therapy has FDA approval, due to challenges in atrial targeting, immune control, and durable expression. Closing this translational gap is critical for future AF gene therapy.
J Cardiovasc Transl Res
· 2025 Dec · PMID 41076491
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Cardiovascular diseases (CVDs) remain the global leading cause of mortality, necessitating novel diagnostics and therapies. Extracellular vesicles (EVs)-including exosomes, microvesicles, and apoptotic bodies-serve as ke...Cardiovascular diseases (CVDs) remain the global leading cause of mortality, necessitating novel diagnostics and therapies. Extracellular vesicles (EVs)-including exosomes, microvesicles, and apoptotic bodies-serve as key intercellular communicators in cardiovascular system. As carriers of bioactive miRNAs/proteins, EVs regulate inflammation, fibrogenesis, angiogenesis, and cardiac/systemic communication. Their non-invasive accessibility and disease-specific molecular signatures enable diagnostic applications. Endogenous origin and targeting capacity make EV ideal drug delivery platforms, while engineering of surface/content properties enhances their therapeutic specificity. However, key challenges persist in reproducibility, long-term safety profiles, clearance mechanisms, and therapeutic applications. Therefore, we highlight the potential of EVs as engineered drug carriers and their therapeutic promise for CVDs such as myocardial infarction, atherosclerosis, and heart failure. Future clinical translation of EV-based tools offers transformative potential-from cardiovascular diagnostics to regenerative therapies-where collaborative efforts will accelerate the pipeline development of these emerging solutions for clinical CVDs management.
Doneda M, Lanzarone E, Pisa FR
… +3 more, Pane B, Pratesi G, Spinella G
J Cardiovasc Transl Res
· 2025 Oct · PMID 41060529
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The aim of this study was to develop and validate a machine learning tool for predicting survival in PAD patients who received surgical treatment. We used the data from 1,615 patients who underwent PAD surgery from 2005...The aim of this study was to develop and validate a machine learning tool for predicting survival in PAD patients who received surgical treatment. We used the data from 1,615 patients who underwent PAD surgery from 2005 to 2020. Gradient boosted decision trees (GBDTs) were used to predict mortality at one, three and five years after the first surgery, while predictor importance was assessed using the SHAP values method. The area under the curve (AUC) of the receiver operating characteristic curve of the one-, three and five-year prediction models were 0.86, 0.84 and 0.80, respectively. Disease stage was the most important predictor, along with age, chronic kidney disease status, hospital length-of-stay and total number of comorbidities. Presence of dyslipidemia was slightly predictive of one- and three-year mortality. Simple clinical and demographic parameters can be used to train a GBDT model capable of predicting PAD follow-up mortality.
Li J, Yi L, Zhang L
… +8 more, Shen L, Lu Y, Wang H, Chen X, Kou Y, Wang Y, Ma R, Teng Z
J Cardiovasc Transl Res
· 2025 Dec · PMID 41051685
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Atherosclerosis (AS) is a chronic inflammatory disease characterized by the formation of fibrous fatty lesions or plaques within the arterial wall, which causes a large amount of morbidity and mortality worldwide. Copper...Atherosclerosis (AS) is a chronic inflammatory disease characterized by the formation of fibrous fatty lesions or plaques within the arterial wall, which causes a large amount of morbidity and mortality worldwide. Copper is a mineral nutrient essential for the human body and is essential for maintaining the normal function of multiple human systems, including the cardiovascular system. Imbalance of copper homeostasis has been increasingly considered as a key factor affecting the pathogenesis and disease progression of AS. This article summarizes the complex association between copper ions and AS, focusing in particular on the key roles of copper metabolism, copper homeostasis and copper death. It aims to reveal the mechanism of action of copper ions in AS and explore treatment strategies targeting copper metabolism, copper death and copper homeostasis imbalance in relation to atherosclerosis, with a view to providing new perspectives and strategies for the treatment and prevention of AS.