Gao M, Pan W, Ma T
… +4 more, Pen Q, Cao R, Zhao C, Yi J
J Cardiovasc Transl Res
· 2025 Aug · PMID 40540207
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Systolic blood pressure variability (SBPV) and arterial stiffness index (ASI) are risk factors for cardiovascular diseases (CVD), but their independent and combined effects remain unclear. This study investigated their a...Systolic blood pressure variability (SBPV) and arterial stiffness index (ASI) are risk factors for cardiovascular diseases (CVD), but their independent and combined effects remain unclear. This study investigated their associations using data from 28,792 UK Biobank participants without CVD at baseline. SBPV and ASI were categorized into quartiles, and Cox regression was used to assess their effects on CVD risk. Over an average follow-up of 12.29 years, 3,967 CVD events occurred. Higher SBPV and ASI were independently associated with increased CVD risk (SBPV Q4: HR 1.25 [1.14-1.38]; ASI Q4: HR 1.24 [1.12-1.36]). A multiplicative interaction was observed (p = 0.019), and their combined effect further elevated risk (SBPV Q4 + ASI Q4: HR 1.63 [1.32-2.02]). These findings suggest SBPV and ASI independently and jointly contribute to CVD risk, highlighting the need for targeted interventions.
J Cardiovasc Transl Res
· 2025 Aug · PMID 40540206
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Despite being recognized for over a century, the athlete's heart (AH) a result of intense and regular physical training remains a topic of clinical debate. This physiological cardiac remodelling involves structural, elec...Despite being recognized for over a century, the athlete's heart (AH) a result of intense and regular physical training remains a topic of clinical debate. This physiological cardiac remodelling involves structural, electrical, and functional changes that can resemble pathological conditions. In some cases, sudden cardiac death may be the first sign of underlying disease. Accurate diagnosis is crucial, but a knowledge gap often exists regarding the normal features of an athlete's heart. Clinical evaluation, including physical examination, personal and family history, and 12-lead electrocardiogram (ECG) findings, plays a key role in identifying conditions such as hypertrophic cardiomyopathy. However, distinguishing between physiological and pathological ECG changes is challenging, potentially leading to either missed diagnoses or unnecessary disqualification. This review outlines the cardiovascular adaptations to training across different athlete groups and emphasizes critical factors in assessing young competitive athletes to ensure safe participation without compromising clinical vigilance.
J Cardiovasc Transl Res
· 2025 Dec · PMID 40536715
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Exosomes are small vesicles secreted by a variety of cells surrounded by a lipid bilayer membrane and containing a variety of biomolecules, of which microRNAs (miRNAs) are the most abundant. Exosomal miRNAs are involved...Exosomes are small vesicles secreted by a variety of cells surrounded by a lipid bilayer membrane and containing a variety of biomolecules, of which microRNAs (miRNAs) are the most abundant. Exosomal miRNAs are involved in the development of cardiovascular diseases(CVD), and their unique biological properties make them expected to be effective targets for the treatment of CVD. This article reviews the biological characteristics, expression, and mechanism of action of exosomes and exosomal miRNAs in CVD, as well as their potential as biomarkers in the diagnosis, treatment, and prognostic assessment of CVD, to provide new ideas in the field of CVD medicine.
Yu L, Neves R, Bos MM
… +4 more, Tester DJ, Sardana M, Giudicessi JR, Ackerman MJ
J Cardiovasc Transl Res
· 2025 Aug · PMID 40526200
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Genetic variants in CACNA1C are associated with several cardiac and neurologic conditions. We conducted a retrospective review of patients evaluated and treated who presented with a pathogenic (P), likely pathogenic (LP)...Genetic variants in CACNA1C are associated with several cardiac and neurologic conditions. We conducted a retrospective review of patients evaluated and treated who presented with a pathogenic (P), likely pathogenic (LP), or variant of uncertain significance (VUS) in CACNA1C. Among 4,774 patients, 49 had P, LP, or VUS variants (55% female; median age 15 years; mean QTc 481 ms). Of these, 22 had long QT syndrome type 8, 8 had Timothy syndrome, 2 had cardiac only Timothy syndrome, and 9 had no cardiac phenotype. Ten patients exhibited extracardiac findings. Thirty-one patients were treated with a beta-blocker, 21 patients had an implantable cardioverter-defibrillator (ICD). Nine patients were on intentional non-therapy. Six patients had at least 1 breakthrough cardiac event on follow-up. Overall, CACNA1C-positive patients present with diverse diagnoses and severity. Treatments vary by phenotype, however management with preventative measures only presents a reasonable option for some phenotype-negative, genotype-positive patients.
Bonini M, Sanjay S, Balmus M
… +6 more, Makkinejad A, Monaghan K, Hirschvogel M, Burris N, Yang B, Nordsletten D
J Cardiovasc Transl Res
· 2025 Aug · PMID 40500547
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Y-incision aortic annular enlargement (Y-AAE) with surgical aortic valve replacement (SAVR) may improve outflow tract hemodynamics and valve-in-valve (ViV) outcomes but could increase thrombosis risk. We used computation...Y-incision aortic annular enlargement (Y-AAE) with surgical aortic valve replacement (SAVR) may improve outflow tract hemodynamics and valve-in-valve (ViV) outcomes but could increase thrombosis risk. We used computational fluid dynamics to analyze post-operative hemodynamics in 15 patient-specific SAVR models, comparing cases with and without Y-AAE. ViV scenarios were simulated by virtually deploying transcatheter aortic valves. Transvalvular peak velocities, pressure gradients, and blood residence time (a proxy for hemostatic risk) were analyzed to assess performance across cases. Y-AAE reduced peak velocity by 39.3% (55% in ViV), transvalvular pressure gradient by 87.2% (92% in ViV), and mean blood residence time by 10.3% (14% in ViV), with no consistent difference in maximum residence time. SAVR with Y-AAE demonstrated improved hemodynamics, even with ViV procedures, and no evidence of increased thrombosis risk.
J Cardiovasc Transl Res
· 2025 Aug · PMID 40498360
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Myocardial ischemia-reperfusion injury (MIRI) is an injury mechanism of myocardial infarction, related to ferroptosis and glycolysis. Lactate produced by glycolysis promotes protein lactylation. This study aimed to inves...Myocardial ischemia-reperfusion injury (MIRI) is an injury mechanism of myocardial infarction, related to ferroptosis and glycolysis. Lactate produced by glycolysis promotes protein lactylation. This study aimed to investigate the correlation between glycolysis, ferroptosis, and GPX4 lactylation in MIRI. Hypoxia/reoxygenation (H/R) increased glucose uptake, lactate production, ECAR, OCR, LDH release, lipid ROS, Fe, GSH, MDA contents, and cell apoptosis, and decreased GSH level in the H9C2 cells, suggesting H/R promoted glycolysis and ferroptosis. 2-DG treatment relieved the H/R-induced injury, while lactate treatment aggravated it. Besides, 2-DG suppressed lactylation of GPX4 at K218 and K228 sites and increased its protein stability. GPX4 overexpression relieved the injury caused by H/R, and alleviated cardiac injury, decreased cardiomyocyte ferroptosis in heart tissues of MIRI rats. In conclusion, GPX4 lactylation facilitated H/R-induced cardiomyocyte injury and aggravated MIRI in rats. Our findings provided new insight into targeting glycolysis and GPX4 lactylation as therapeutic strategies of MIRI.
Stolen CM, Kupfer ME, Tomes K
… +5 more, Horan S, Pandey A, Snodie J, Frost K, Merhaut S
J Cardiovasc Transl Res
· 2025 Aug · PMID 40478435
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Integration into clinical workflow remains a barrier to realizing the benefits of remote heart failure monitoring technologies. A workflow redesign program was conducted at 27 cardiology sites to improve implementation o...Integration into clinical workflow remains a barrier to realizing the benefits of remote heart failure monitoring technologies. A workflow redesign program was conducted at 27 cardiology sites to improve implementation of heart failure remote monitoring with HeartLogic. Device data was retrospectively retrieved from HeartLogic-capable ICDs and CRT-Ds for the 12-month periods before and after re-design. Workflow redesign led to a decrease in HeartLogic enablement time (28±110 to 10±31 days, p<0.0001) and reduction in delayed data transmissions (10% to 6%). The number of HeartLogic alert onsets per year was unchanged; however, the length of individual alerts decreased from pre- to post-redesign (47.6±38.4 to 44.1±36.5 days, p=0.001) as did the percentage of time patients spent in alert (15.5±19.9% to 14.3±19.0%, p=0.04). The maximum HeartLogic index values per alert were also lower post-redesign (28.9±12.8 vs 27.8±12.1, p=0.001). Workflow redesign improved remote monitoring utilization and heart failure alert metrics.
J Cardiovasc Transl Res
· 2025 Aug · PMID 40465194
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Diabetic myocardial disorder is characterized by myocardial dysfunction in diabetes mellitus patients, independent of other heart disease causes like coronary artery disease or hypertension. This condition threatens the...Diabetic myocardial disorder is characterized by myocardial dysfunction in diabetes mellitus patients, independent of other heart disease causes like coronary artery disease or hypertension. This condition threatens the well-being of patients. At the cellular and molecular levels, disruptions in cardiomyocyte metabolism, abnormal calcium signaling, and increased reactive oxygen species production, among others, interconnect to create a complex pathological network that worsens myocardial cell damage and leads to cardiac dysfunction symptoms. The limited effectiveness of current pharmacological treatments has increased the appeal of non-pharmacological therapies, especially exercise therapy. Exercise is anticipated to ameliorate diabetic myocardial disease through pleiotropic beneficial effects. The fundamental mechanisms behind these benefits remain unclear; further investigation of these mechanisms will aid in developing targeted therapies. This paper aims to explore how exercise affects myocardial metabolism, antioxidant capacity, fibrosis, and microangiopathy while providing an overview of key mechanisms and recent breakthroughs to encourage ongoing research in this area.
Xue Y, Jia Z, Liang S
… +4 more, Dai M, Liu F, Wu J, Zhao R
J Cardiovasc Transl Res
· 2025 Dec · PMID 40465193
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Early diagnosis and treatment of atrial cardiomyopathy(ACM) are crucial for patients with atrial fibrillation(AF), and further exploration of its biomarkers remains necessary. High-throughput sequencing of exosomal miRNA...Early diagnosis and treatment of atrial cardiomyopathy(ACM) are crucial for patients with atrial fibrillation(AF), and further exploration of its biomarkers remains necessary. High-throughput sequencing of exosomal miRNAs was performed on blood samples from patients with persistent AF (PeAF) exhibiting mild and severe left atrial fibrosis, with supraventricular tachycardia (SVT) patients. Quantitative real-time reverse transcription polymerase chain reaction analysis validated differentially expressed miRNAs (DE miRNAs) from severe left atrial fibrosis PeAF, SVT and health controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted on target genes. Four exosomal DE miRNAs were identified, including miR-5106, let-7e-5p, miR-320c, and miR-382-3p. Exosomal miR-320c was down-regulated in severe left atrial fibrosis PeAF patients, while the other three miRNAs showed no significant changes. Exosomal miR-320c emerges as a potential biomarker for severe left atrial fibrosis and ACM, suggesting its suitability as a therapeutic target.
J Cardiovasc Transl Res
· 2025 Aug · PMID 40457137
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The endothelial glycocalyx layer forms interface between the luminal surface and circulating blood, and consists of cell surface membrane-bound glycosaminoglycan chains and transmembrane embedded glycoproteins and proteo...The endothelial glycocalyx layer forms interface between the luminal surface and circulating blood, and consists of cell surface membrane-bound glycosaminoglycan chains and transmembrane embedded glycoproteins and proteoglycans, such as glypicans and syndecans. This dynamic layer contributes to various endothelial functions, including maintenance of vascular permeability, mechanosensation, shear-stress-mediated nitric oxide generation, modulation of interactions with constituents of blood, and regulation of vascular tone. Following vascular device placement, the transmembrane-linked glycosaminoglycan side chains are damaged and released into the circulation as soluble heparan sulfate, hyaluronan, and chondroitin sulfate. Damage to the glycocalyx causes an increase in vascular permeability, adhesion of leukocytes and platelets to the endothelium, extravasation of proinflammatory cells, dysregulation of vascular tone, imbalance of coagulation, and loss of antioxidant defense mechanisms. This review highlights the function of the endothelial glycocalyx as a vasoprotective layer and discusses targeted therapeutic approaches to promoting the restoration of glycocalyx disrupted by vascular stent implantation.
Zhao X, Song Y, Zhang L
… +3 more, Wang L, Zhao X, Wang J
J Cardiovasc Transl Res
· 2025 Aug · PMID 40457136
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The accuracy of prevalent risk models recommended by American Heart Association/American College of Cardiology(AHA/ACC) and European Society of Cardiology(ESC) for hypertrophic cardiomyopathy(HCM) patients is suboptimal....The accuracy of prevalent risk models recommended by American Heart Association/American College of Cardiology(AHA/ACC) and European Society of Cardiology(ESC) for hypertrophic cardiomyopathy(HCM) patients is suboptimal. We assessed the utility of cardiac magnetic resonance(CMR)-3D left ventricular mechanical dispersion(LVMD) in the prognostic stratification of 159 HCM and explore the correlation with myocardial fibrosis heterogeneity. Entropy demonstrated linear correlations with 3D LVMD. Patients experienced endpoint events exhibited significantly higher radial LVMD(LVMD-R), circumferential LVMD(LVMD-C), and longitudinal LVMD(LVMD-L). Kaplan-Meier analyses demonstrated that HCM patients with elevated LVMD had a higher risk of primary and secondary endpoint events. In multivariable Cox analysis incorporated the guidelines risk classification, both LVMD-C and LVMD-L emerged as significant predictors for endpoint events. We developed a model incorporated the 2022 ESC risk stratification in combination with LVMD-C and LVMD-L and revealed that combined model significantly outperformed the guidelines alone. Additionally, entropy demonstrated linear correlations with LVMD.
J Cardiovasc Transl Res
· 2025 Dec · PMID 40457135
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As one of the leading causes of death globally, early diagnosis and prevention of cardiovascular disease have become the focus of clinical and public health. Extracellular vesicles (EVs) are small, double-layered membran...As one of the leading causes of death globally, early diagnosis and prevention of cardiovascular disease have become the focus of clinical and public health. Extracellular vesicles (EVs) are small, double-layered membrane structures actively secreted by cells and are widely present in body fluids such as blood, urine, and saliva. They carry various bioactive molecules, including proteins and nucleic acids, and are known for their remarkable stability and easy accessibility, making them promising candidates for identifying cardiovascular disease. This review summarizes the applications of EVs in the early diagnosis of cardiovascular disease, explores the potential biomarkers of proteins and RNAs (such as miRNA, lncRNA, and circRNA) contained within EVs, and discusses the prospects and challenges of EV biomarkers in clinical applications.
J Cardiovasc Transl Res
· 2025 Aug · PMID 40439867
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To investigate the role of miR-139-5p in acute coronary syndrome (ACS), serum miR-139-5p levels were measured via quantitative real-time polymerase chain reaction (qRT-PCR) in 117 ACS patients, 91 stable angina (SAP) pat...To investigate the role of miR-139-5p in acute coronary syndrome (ACS), serum miR-139-5p levels were measured via quantitative real-time polymerase chain reaction (qRT-PCR) in 117 ACS patients, 91 stable angina (SAP) patients, 89 healthy controls. Its associations with ACS severity, major adverse cardiovascular events (MACE) were evaluated using statistical tests, Kaplan-Meier survival, COX regression analysis. Effect of miR-139-5p on cell function and inflammation in oxidized low-density lipoprotein (ox-LDL) -induced human coronary artery smooth muscle cells (HCASMCs) was evaluated in vitro. Upregulated miR-134-5p in ACS distinguished ACS from SAP/health individuals, correlating with increased cardiac troponin I (cTnI), Gensini score, MACE risk. COX regression identified miR-139-5p as independent ACS prognostic factors. In vitro, miR-139-5p downregulation suppressed ox-LDL-induced HCASMC proliferation, migration, and inflammation. Upregulated miR-139-5p expression showed a diagnostic and prognostic value on ACS and was correlated with ACS severity. Downregulated miR-139-5p expression exhibited a suppressive effect on ACS progression.
Rahimi F, Löffelhardt N, Minners J
… +16 more, Breitbart P, Franke K, Hartikainen TS, Valina C, Mühlen CVZ, Nührenberg T, Kastrati A, Woitek F, Elsaesser A, Abdel-Wahab M, Sossalla S, Hochholzer W, Westermann D, Neumann FJ, Olivier C, Ferenc M
J Cardiovasc Transl Res
· 2025 Aug · PMID 40425928
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Whether culotte or double kissing (DK)-crush stenting is the superior systematic 2-stent technique in non-left main bifurcation lesions is unclear. The BBK-3 (unique identifier NCT04192760) is a multicenter, prospective,...Whether culotte or double kissing (DK)-crush stenting is the superior systematic 2-stent technique in non-left main bifurcation lesions is unclear. The BBK-3 (unique identifier NCT04192760) is a multicenter, prospective, randomized controlled trial to test the hypothesis that culotte stenting reduces maximal percent diameter restenosis at 9-month follow-up compared to DK-crush stenting in de-novo non-left main coronary bifurcation lesions using approved, third-generation drug-eluting stents (DES). A total of 400 patients will be randomized in a 1:1 ratio to receive a two-stent strategy. The primary study endpoint is the maximal percent diameter in-stent restenosis within the bifurcation at 9 months, assessed by quantitative coronary angiography. Secondary endpoints include target lesion revascularization (TLR), the composite of death and myocardial infarction, emergent cardiac bypass surgery and TLR (MACE) at 12 months. BBK-3 will assist in the identification of the preferable, contemporary 2-stent strategy in the treatment of de-novo non-left main coronary bifurcation lesions.
Wang J, Hu Y, Yang X
… +9 more, Xu R, Chen Z, Wang Z, Ma L, Zhang F, Leng X, Ge J, Xiang J, Li C
J Cardiovasc Transl Res
· 2025 Jun · PMID 40388093
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Coronary flow reserve (CFR) is a key parameter for risk stratification in coronary artery disease but is limited by high cost, prolonged procedure time, and suboptimal reproducibility. We proposed a novel angiography-bas...Coronary flow reserve (CFR) is a key parameter for risk stratification in coronary artery disease but is limited by high cost, prolonged procedure time, and suboptimal reproducibility. We proposed a novel angiography-based method (Angio-CFR) to overcome these challenges and assessed its diagnostic performance. 107 consecutive patients underwent invasive coronary angiography with thermodilution-derived CFR (CFR) were prospectively enrolled. Flow velocity at hyperemia and rest was estimated from angiographic images, and Angio-CFR was calculated as their ratio. Angio-CFR correlated well with CFR (r = 0.72, p < 0.001), and showed good discrimination of CFR < 2.5 (AUC = 0.879, p < 0.001) with an optimal cut-off of 2.5. The accuracy, sensitivity, and specificity of Angio-CFR were 81.71%, 83.33%, and 81.25%, respectively. Angio-CFR provides a pressure-wire-free method for coronary function assessment, demonstrating promising diagnostic accuracy and offering a more accessible approach for CFR measurement in clinical practice.
Racodon M, Fabre C, Vanhove P
… +5 more, Vale JD, Bolpaire R, Moutailler E, Malanda F, Secq A
J Cardiovasc Transl Res
· 2025 Aug · PMID 40341471
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The Six-Minute Walk Test (6MWT) traditionally assesses exercise capacity in cardiac patients but requires a large space. The Six-Minute Stepper Test (6MST) has been validated as an alternative in various populations. Thi...The Six-Minute Walk Test (6MWT) traditionally assesses exercise capacity in cardiac patients but requires a large space. The Six-Minute Stepper Test (6MST) has been validated as an alternative in various populations. This study evaluates the reproducibility, sensitivity, and validity of the 6MST in 60 cardiac patients (15 women, 45 men, 58 ± 11.2 years). Participants underwent cardiopulmonary exercise tests (CPET), two 6MSTs, and one 6MWT at the start and end of cardiac rehabilitation (CR). Performance in the 6MST improved significantly after CR (343 ± 89.0 vs. 451 ± 105.6 steps, p < 0.0001). The 6MST showed moderate correlation with the 6MWT and CPET (r = 0.54, p < 0.0001). Dyspnoea and leg fatigue were higher in the 6MST than in the 6MWT (p < 0.0001). Conclusion: The 6MST is a safe, valid, sensitive, and reproducible tool for evaluating exercise capacity in cardiac patients, comparable to the 6MWT.
Mai B, Jiang W, Yang J
… +10 more, Chen Y, Qin Z, Li Y, Tu W, Lin Y, Chan WS, Wu J, Cheng F, Xu T, Xie S
J Cardiovasc Transl Res
· 2025 Dec · PMID 40338502
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Treg dysfunction in ischemic cardiomyopathy (ICM) remains mechanistically unclear. We investigated ICM plasma small extracellular vesicles (ICM-sEVs) in Treg regulation and post-MI remodeling. Flow cytometry assessed Tre...Treg dysfunction in ischemic cardiomyopathy (ICM) remains mechanistically unclear. We investigated ICM plasma small extracellular vesicles (ICM-sEVs) in Treg regulation and post-MI remodeling. Flow cytometry assessed Treg frequency. ICM-sEV miRNA sequencing revealed miR-223-3p enrichment, validated using miR-223 and Foxp3 mice. ICM patients and mice exhibited elevated Treg numbers but suppressed Foxp3. miR-223-3p was upregulated in ICM-sEVs and inversely correlated with functional Tregs. ICM-sEVs administration aggravated ventricular remodeling post myocardial infarction (MI) in mice while reducing Treg frequency and elevating miR-223-3p in vitro. miR-223 knockdown increased Treg cell number and Foxp3 expression, whereas miR-223 overexpression reversed the phenotype. ICM-sEVs aggravate ventricular remodeling post-MI and promote miR-223-3p-mediated Treg cell dysfunction.
Zhang J, Xu Y, Han Z
… +4 more, Liu B, Wang M, Bao L, He Y
J Cardiovasc Transl Res
· 2025 Jun · PMID 40293654
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To explore the function and potential mechanism of laccase domain-containing 1 (LACC1) on atherosclerosis (AS). ApoE mice feed with high-fat diet (HFD) were injected with adenovirus shLACC1 (Ad-shLACC1) or Ad-shNC via ta...To explore the function and potential mechanism of laccase domain-containing 1 (LACC1) on atherosclerosis (AS). ApoE mice feed with high-fat diet (HFD) were injected with adenovirus shLACC1 (Ad-shLACC1) or Ad-shNC via tail vein. LACC1 was highly expressed in macrophages of atherosclerotic plaque in ApoE mice and ox-LDL-treated Raw264.7 macrophages. LACC1 silencing enhanced AS development and facilitated inflammation in mice. Then, we found that LACC1 silencing facilitated inflammation but repressed polyamine immunometabolism in ox-LDL-treated Raw264.7 macrophages. Through rescue experiments using ornithine or ODC1 inhibitor (DFMO), we further confirmed that LACC1 promoted polyamine immunometabolism to inhibit inflammation in ox-LDL-treated Raw264.7 macrophages. In addition, the observed LACC1 function was dependent on NOS2. In conclusion, we proved that the downregulation of LACC1 promoted AS progression via inhibiting polyamine immunometabolism in inflammatory macrophages, suggesting LACC1 may be a potential therapeutic target for AS.
J Cardiovasc Transl Res
· 2025 Jun · PMID 40261542
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This study investigated the association between serum small peptides and arteriosclerosis (AS) in hypertensive patients. Sixty hypertensive patients (with and without AS) and 30 healthy individuals were enrolled. Untarge...This study investigated the association between serum small peptides and arteriosclerosis (AS) in hypertensive patients. Sixty hypertensive patients (with and without AS) and 30 healthy individuals were enrolled. Untargeted metabolomics identified 120 peptides in AS patients, 136 in hypertensive patients, and 59 shared peptides. LASSO regression identified key peptides differentiating hypertensive patients with AS from those without. Peptides like Thr-Ile, Phe-Asp-Lys, and Lys-Ile-Val-Lys were upregulated in AS, while others like Gln-Glu and Lys-Lys were higher in non-AS patients. The diagnostic model showed AUCs of 0.896 for AS and 0.909 for non-AS. Elevated levels of Lys-Ile-Val-Lys and Phe-Asp-Lys were linked to increased carotid intima-media thickness, indicating higher AS risk.
Chen LS, Koh G, Wang YN
… +6 more, Kim GW, Singh Z, Lehnert A, Miyaoka R, Gurm HS, Maxwell AD
J Cardiovasc Transl Res
· 2025 Jun · PMID 40259194
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Peripheral artery disease results in ischemia necessitating interventions such as balloon angioplasty. However, calcified lesions resist balloon and stent expansion, leading to poor outcomes. We hypothesized that focused...Peripheral artery disease results in ischemia necessitating interventions such as balloon angioplasty. However, calcified lesions resist balloon and stent expansion, leading to poor outcomes. We hypothesized that focused ultrasound can fracture vascular calcifications and enable balloon angioplasty. In a first experiment, focused ultrasound was applied to ex vivo human calcified plaque specimens to determine its effects based on micro-CT imaging. In a second experiment, ultrasound was applied to an in vitro phantom to evaluate whether the effects enable balloon expansion. Fractures, thinning, and disintegration of calcified sections were observed in 15 of 18 treated human plaque samples. Minor mechanical disruption to soft plaque was found in 33% of samples. In tissue phantoms, n = 10/10 samples were successfully expanded by a water-filled angioplasty balloon with ultrasound applied prior to or during expansion. No controls (n = 0/10) were expanded. These results indicate focused-ultrasound plaque fracture is feasible and may enhance balloon angioplasty.