J Cardiovasc Transl Res
· 2025 Dec · PMID 40839179
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Vascular endothelial growth factor receptor 1 (VEGFR1) is a key regulator of endothelial function, angiogenesis, inflammation, and cardiomyocyte survival, with both beneficial and deleterious effects in cardiovascular di...Vascular endothelial growth factor receptor 1 (VEGFR1) is a key regulator of endothelial function, angiogenesis, inflammation, and cardiomyocyte survival, with both beneficial and deleterious effects in cardiovascular disease. In this review, we provide some key information on the molecular biology governing VEGFR1 function, its role in cardiovascular diseases and describe gene therapy strategies targeting either membrane-bound or its soluble isoform sFLT1 to treat these diseases. Clinical Relevance Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Thus, new therapeutic targets and strategies are warranted to mitigate CVDs economic and societal burdens. Members of the Vascular Endothelial Growth Factor (VEGF) family and their receptors stand as key players in the majority of biological processes underlying CVDs, including inflammation, angiogenesis, and cardiomyocyte function. This review focuses on the role of VEGFR1 in the onset and progression of the most common CVDs, with particular emphasis on the signaling mechanisms occurring in different cell types, and discusses its potential as a target for gene therapy.
J Cardiovasc Transl Res
· 2025 Dec · PMID 40825915
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Cardiovascular disease (CVD) is a prominent contributor to global mortality rates, and its prevalence is consistently on the rise. The utilization of deep sequencing-based transcriptome profiling methodologies has yielde...Cardiovascular disease (CVD) is a prominent contributor to global mortality rates, and its prevalence is consistently on the rise. The utilization of deep sequencing-based transcriptome profiling methodologies has yielded empirical support for the notion that the transcriptional activity of the human genome is more expansive than previously postulated. Long Non-Coding RNAs (lncRNAs) are a heterogeneous collection of noncoding transcripts with a length exceeding 200 nucleotides. Transposable elements represent a significant proportion of the human genome, and their potential contribution could be as high as 90%. LncRNAs can exert control over several biological processes through their ability to modulate the transcriptional activity of coding genes, engage in direct protein interactions, and potentially encode proteins. lncRNAs have been acknowledged as significant factors in the causation and progression of myocardial infarction, heart failure, cardiac hypertrophy, arrhythmias, and other pathological processes that have a considerable influence on the prognosis and survival of individuals afflicted with CVD. Moreover, the observable patterns of expression demonstrated by lncRNAs in different CVD scenarios greatly augment their potential as biomarkers and targets for intervention. To lay a strong foundation for future research on the mitigation and management of CVDs, we comprehensively examine current scholarly literature on lncRNAs in the context of cardiovascular disorders. The discourse also involves the potential usefulness of lncRNAs as biomarkers and targets for therapeutic interventions.
J Cardiovasc Transl Res
· 2025 Oct · PMID 40825914
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Cardiac fibrosis, marked by excessive extracellular matrix accumulation, is a key endpoint in various cardiac diseases and is linked to energy metabolic disorders. This review explores the relationship between mitochondr...Cardiac fibrosis, marked by excessive extracellular matrix accumulation, is a key endpoint in various cardiac diseases and is linked to energy metabolic disorders. This review explores the relationship between mitochondrial energy metabolism and cardiac fibrosis, focusing on the metabolic reprogramming in fibroblasts and cardiomyocytes during fibrosis development. We examine changes in substrate utilization, oxidative phosphorylation (OXPHOS), and ATP production that characterize the fibrotic heart. The metabolic dysregulation involves disruptions in fatty acid oxidation, glucose metabolism, and amino acid metabolism, contributing to fibrosis pathogenesis. Additionally, we discuss the implications of these metabolic alterations for therapeutic strategies, highlighting the potential of targeting energy metabolism to reverse or halt cardiac fibrosis progression. By synthesizing current knowledge and identifying research gaps, this review aims to lay the groundwork for future studies and enhance therapeutic approaches for this challenging condition.
Rezaeitaleshmahalleh M, Lyu Z, Mu N
… +3 more, Nainamalai V, Pandey A, Jiang J
J Cardiovasc Transl Res
· 2025 Oct · PMID 40815368
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Temporal velocity-informatics (TVI) is a novel technique utilizing spatial analysis of time-resolved 3D velocity fields to quantify flow disturbance in vascular aneurysms. Although it can improve the characterization of...Temporal velocity-informatics (TVI) is a novel technique utilizing spatial analysis of time-resolved 3D velocity fields to quantify flow disturbance in vascular aneurysms. Although it can improve the characterization of intracranial aneurysms' (IA) rupture status, calculation of time-resolved 3D velocity fields using computational fluid dynamics (CFD) simulations limits its clinical translation. This study aims to test the feasibility of using IA's geometrical information in conjunction with machine learning (ML)-based regression methods to predict TVI parameters. The effectiveness of these ML-predicted TVI parameters in predicting IA's rupture status was evaluated using one hundred twelve IAs with known rupture status. We found that predicting the IA's rupture status using predicted TVI can achieve an AUC of 0.88, and a total accuracy of 81.6%. Also, We found that the consistency between ML-predicted TVI variables and estimated TVI metrics calculated from CFD-simulated velocity data was higher than our ability to predict wall shear stress-based metrics.
Wild L, Beele A, Seguchi M
… +6 more, Lenz T, Nicol P, Sabic-Halilcevic E, Klosterman GR, Kastrati A, Joner M
J Cardiovasc Transl Res
· 2025 Oct · PMID 40815367
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We aimed to evaluate a novel polymer-free hybrid drug eluting stent (DES) relative to benchmark devices and specific controls addressing singular components of the test device in a juvenile pig model of coronary stenting...We aimed to evaluate a novel polymer-free hybrid drug eluting stent (DES) relative to benchmark devices and specific controls addressing singular components of the test device in a juvenile pig model of coronary stenting. 80 stents were implanted in 28 juvenile pigs and evaluated at 28 and 90 days using quantitative coronary angiography and histopathology (n = 10 per group). Scanning electron microscopy was used at 14 days to assess early re-endothelialization (n = 3 per group). The test device featured a cobalt-chromium (CoCr) backbone with a polymer-free probucol matrix releasing everolimus. The polymer-free test stent showed improved strut coverage at 28 days compared to the polymer-coated control, with significantly lower neointimal growth at 90 days and near complete endothelialization at 14 days. This preclinical study supports the favorable vascular healing profile of a polymer-free hybrid DES, warranting further clinical investigation.
Wattanachayakul P, Kittipibul V, Yaranov DM
… +2 more, Miller WL, Fudim M
J Cardiovasc Transl Res
· 2025 Oct · PMID 40794357
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Assessment of volume status is essential in heart failure (HF) management, yet the relationship between cardiac filling pressures and true intravascular volume remains unclear, especially in patients with obesity. We ana...Assessment of volume status is essential in heart failure (HF) management, yet the relationship between cardiac filling pressures and true intravascular volume remains unclear, especially in patients with obesity. We analyzed 262 ambulatory HF patients who underwent blood volume analysis (BVA) and same-day right heart catheterization. Patients were stratified by BMI into non-obese (n = 104), obese (n = 121), and morbidly obese (n = 37). Cardiac filling pressures showed modest correlations with directly measured total blood volume (TBV); RAP correlated with TBV %deviation (r = 0.36-0.58), while PCWP correlations were weaker (r = 0.19-0.36) and non-significant in morbidly obese patients. Concordance between pressure and volume was highest in non-obese patients (RAP/TBV 79.8%, PCWP/TBV 69.2%) and lower in obese (66.1%, 55.4%) and morbidly obese individuals (64.9%, 67.6%). Approximately one-third or more of obese patients exhibited discordant pressure-volume profiles. These findings suggest that in obesity, cardiac filling pressures may not reliably reflect volume status.
Chen W, Fan Y, Ren L
… +5 more, Li F, Tan X, Wang X, Du J, Wang Y
J Cardiovasc Transl Res
· 2025 Oct · PMID 40745245
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Heart failure with mildly-reduced ejection fraction (HFmrEF) lacks therapeutic strategies due to heterogeneity and dynamic transitions between HFrEF/HFpEF. Proteins constitute predominant drug targets and primary mediato...Heart failure with mildly-reduced ejection fraction (HFmrEF) lacks therapeutic strategies due to heterogeneity and dynamic transitions between HFrEF/HFpEF. Proteins constitute predominant drug targets and primary mediators of signaling pathways in HF. We measured 92 plasma proteins (Olink CardiovascularIII) in 230 HF patients from BIOMS-HF registry. Fifteen, eighteen, and fifteen baseline proteins discriminated MACEs were determined in HFmrEF, HFpEF, and HFrEF, respectively. Pathway enrichment revealed shared signaling in HFmrEF/HFpEF (apoptosis, etc.), HFmrEF/HFrEF (vascular regulation, etc.), and HFmrEF/HFrEF/HFpEF (inflammatory/hormonal signaling). Four patient phenotypes were identified according to proteomic signatures using unsupervised learning: Cluster1 (younger, smokers, lowest MACEs [29.5%]); Cluster2 (elderly, higher comorbidity, diastolic dysfunction); Cluster3 (systolic dysfunction, elevated heart rates, responsive to HFrEF therapies); Cluster4 (high inflammation, cardiometabolic disturbances, highest MACEs [74.4%]). Cross-referenced with druggable genome database, TNF-R1 was revealed as an appealing druggable target for cluster2/4, while OPN and MMP-2 for cluster3/4. Unsupervised learning based on proteomics identified four HFmrEF phenotypes, each providing druggable targets according to distinct pathophysiological pathways.
He T, Sha J, Hu Y
… +5 more, Shao C, Zhou Y, Chen L, Yao J, Gao J
J Cardiovasc Transl Res
· 2025 Oct · PMID 40711504
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The heart grows in response to both pathological and physiological stimuli. Pathological hypertrophy often leads to cardiomyocyte loss and heart failure (HF), whereas physiological hypertrophy paradoxically protects the...The heart grows in response to both pathological and physiological stimuli. Pathological hypertrophy often leads to cardiomyocyte loss and heart failure (HF), whereas physiological hypertrophy paradoxically protects the heart. Comparing these two types of hypertrophy can elucidate the differences and connections in their molecular mechanisms, which is pivotal for unraveling the pathogenesis of HF. This study compares pathological (TAC-induced) and physiological (exercise-induced) cardiac hypertrophy using single-cell and bulk transcriptomics. Mitochondrial fusion/fission imbalance emerged as a key dysregulated pathway in both models. An early increase in the fusion/fission ratio (2 weeks post-TAC) resembled exercise-induced remodeling, while a progressive decline at 5-8 weeks marked transition to pathological hypertrophy. By 11 weeks, suppressed fusion and increased fission led to heart failure. Downregulation of fusion genes (Mfn1, Mfn2, Opa1) and upregulation of fission genes (Fis1, Dnm1l) highlight mitochondrial dynamics as critical drivers of disease progression.
J Cardiovasc Transl Res
· 2025 Oct · PMID 40705203
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Cardiometabolic diseases (CMD) encompass a cluster of cardiovascular disorders primarily driven by metabolic dysregulation, such as obesity-associated cardiomyopathy, hypertensive heart disease, and diabetic cardiomyopat...Cardiometabolic diseases (CMD) encompass a cluster of cardiovascular disorders primarily driven by metabolic dysregulation, such as obesity-associated cardiomyopathy, hypertensive heart disease, and diabetic cardiomyopathy. The pathogenesis of CMD is closely linked to chronic inflammation, myocardial hypertrophy, and mitochondrial energy metabolism dysfunction. Recently, the succinate-GPR91 pathway, a critical hub for metabolic regulation, has gained attention for its role in CMD. In addition to its function as an intermediate in the TCA cycle, succinate also exerts a range of pathophysiological effects by acting as a signaling molecule through the activation of its receptor, GPR91.Studies indicate that in metabolic disorders such as obesity, hypertension, diabetes,and atherosclerosis, abnormal activation of the succinate-GPR91 axis exacerbates inflammation, accelerates myocardial hypertrophy, and induces mitochondrial dysfunction, contributing to cardiovascular damage. Targeting the succinate-GPR91 pathway may offer novel CMD therapies. This article reviews succinate's role in inflammation, hypertrophy, mitochondrial dysfunction, and other diseases, offering insights for CMD research and treatment.
Mao YA, Wang R, Shi X
… +8 more, Jin Y, Pan Z, Chatterjee E, Li G, Chen X, Wang H, Jiang J, Xiao J
J Cardiovasc Transl Res
· 2025 Oct · PMID 40699512
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Myocardial infarction (MI), is a leading cause of global mortality, marked by cardiomyocyte death. This takes place as a result of ischemic injury, the detrimental impacts of oxidative stress, and inflammatory responses....Myocardial infarction (MI), is a leading cause of global mortality, marked by cardiomyocyte death. This takes place as a result of ischemic injury, the detrimental impacts of oxidative stress, and inflammatory responses. Conventiona pharmacological interventions, are unfortunately limited by a relatively low targeting efficiency and the inability to reverse the fate of cardiomyocyte death. Recent advances in nanotechnology have led to the development of multifunctional nanoparticles, offering innovative solutions to effectively address these complex challenges. These nanoscale platforms have the remarkable capability to enable targeted drug delivery, precisely regulate the microenvironment, and facilitate real-time monitoring of the cardiac repair processes. This development represents a substantial paradigm shift in the treatment of MI. This review integrates the crucial findings obtained from the recent studies focusing on nanoparticle-based strategies for multifunctional cardiac repair after MI, aiming to explore the potential of nanoparticles in the treatment of MI.
Ferreira Felix I, Karlinski Vizentin V, Alzate-Aguirre M
… +8 more, Patel M, Geske JB, Araoz P, Giudicessi JR, Ommen SR, Arruda-Olson AM, Ackerman MJ, Bos JM
J Cardiovasc Transl Res
· 2025 Oct · PMID 40699511
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This study aimed to evaluate the role of cardiac magnetic resonance (CMR) in updating The Mayo Clinic Hypertrophic Cardiomyopathy (HCM) Genotype Predictor Score. We performed an analysis of 175 HCM patients with an echoc...This study aimed to evaluate the role of cardiac magnetic resonance (CMR) in updating The Mayo Clinic Hypertrophic Cardiomyopathy (HCM) Genotype Predictor Score. We performed an analysis of 175 HCM patients with an echocardiogram, CMR, and genetic test at the Mayo Clinic (2004 to 2018). Yield of a positive genetic test for the original echocardiogram-based score ranged from 38% (-1 point) to 100% (4 or 5 points), with an AUC of 0.659. Late gadolinium enhancement (LGE) presence was a strong predictor of positive genetic test (p = 0.002) and was added to the original score to create the updated version. The yield of positive genetic test for the updated score ranged from 25% (-1 point) to 100% (5 or 6 points) (p < 0.001), with an AUC of 0.724 and significant increase in diagnostic accuracy (p = 0.03). The updated genotype predictor score had improved accuracy when compared to the prior version.
Liu J, Bai C, Yang H
… +8 more, Song L, Xu H, Sun Y, Suo M, Gao Z, Li H, Wang F, Chen J
J Cardiovasc Transl Res
· 2025 Aug · PMID 40694178
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Ischemic stroke (IS) is the most common subtype of stroke. However, reliable blood biomarkers for early diagnosis remain unavailable. This study developed a predictive model based on peripheral blood (PB) biomarkers. PB...Ischemic stroke (IS) is the most common subtype of stroke. However, reliable blood biomarkers for early diagnosis remain unavailable. This study developed a predictive model based on peripheral blood (PB) biomarkers. PB samples from two independent cohorts including IS patients and healthy controls (CTR) were analyzed by RNA sequencing (RNA-seq). 69 mRNAs were consistently and significantly dysregulated in IS patients. Functional enrichment analysis revealed that the IS phenotype was negatively associated with NK cell-mediated cytotoxicity and single-sample gene set enrichment analysis (ssGSEA) revealed a significant reduction in Cd56 NK cells, Cd56 NK cells, and NKT cells in IS patients. A four-gene diagnostic model-BCL2A1, FAM200B, IGJ, and TXN-was identified and exhibited high diagnostic accuracy across derivation, validation, and external cohorts (AUCs: 0.94, 0.91, and 0.96, respectively). Additionally, potential small molecule compounds were screened using Enrichr database, among which cytochalasin D may represent a novel candidate drug for IS treatment.
Szymczak A, Skwarek-Dziekanowska A, Sobieszek G
… +2 more, Małecka-Massalska T, Powrózek T
J Cardiovasc Transl Res
· 2025 Oct · PMID 40694177
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Cachexia is a complex syndrome often affecting chronic heart failure (CHF) patients, characterized by muscle wasting and systemic inflammation. Early detection is crucial for improving patient outcomes. This study evalua...Cachexia is a complex syndrome often affecting chronic heart failure (CHF) patients, characterized by muscle wasting and systemic inflammation. Early detection is crucial for improving patient outcomes. This study evaluated candidate inflammatory and nutritional biomarkers, including a novel C-reactive protein-to-albumin ratio (CAR) modification adjusted for body mass index (CARB), in predicting cachexia and muscle depletion in CHF patients. By analyzing 154 newly diagnosed CHF patients, 25 candidate inflammatory-nutritional biomarkers were examined. Muscle depletion parameters (fat-free mass-FFM, fat-free mass index-FFMI, appendicular lean mass-ALM, appendicular skeletal muscle-ASM) were assessed using bioelectrical impedance analysis and the Global Leadership Initiative on Malnutrition (GLIM) criteria. CARB was found to be the most significant predictor of cachexia (OR = 4.89) and muscle mass reduction (OR = 2.450 for FFMI; OR = 3.530 for ASMI). CARB demonstrated excellent diagnostic accuracy (AUC = 0.930) and is a promising candidate biomarker for predicting cachexia and muscle depletion in CHF.
J Cardiovasc Transl Res
· 2025 Oct · PMID 40691390
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Atherosclerosis (AS) is a vascular disorder characterized by lipid accumulation, fibrous tissue proliferation, and calcium deposition in the intima, contributing significantly to the mortality associated with cardiovascu...Atherosclerosis (AS) is a vascular disorder characterized by lipid accumulation, fibrous tissue proliferation, and calcium deposition in the intima, contributing significantly to the mortality associated with cardiovascular disease, and the pathogenesis of AS is multifaceted. Recent studies have identified copper (Cu) overlap induced cuproptosis as a key mechanism underlying cellular dysfunction in AS. Cuproptosis impacts the function and survival of multiple cell types within AS lesions by several downstream pathways, and regulating cellular cuproptosis may be a very promising clinical treatment strategy. In this review, we explored the influence of key regulatory proteins and signaling pathways associated with copper homeostasis and cuproptosis in AS, and the potential regulators of cuproptosis in AS therapy, especially the endogenous metabolites, copper ionophore, Cu oxide nanoparticles and natural products, we also discuss emerging therapeutic strategies and offering insights into future developments and translational medicine or challenge by targeting cuproptosis in AS pathogenesis.