{"title":"Roles of Lipoxygenases in Cardiovascular Diseases.","authors":"Ting Liu, Ding Ai","doi":"10.1007/s12265-025-10605-2","DOIUrl":"10.1007/s12265-025-10605-2","url":null,"abstract":"<p><p>Lipoxygenases (LOXs) are a family of dioxygenases that catalyze the peroxidation of polyunsaturated fatty acids, such as linoleic acid and arachidonic acid, initiating the synthesis of bioactive lipid mediators. The LOX-mediated production of these bioactive molecules in various cell types plays a critical role in the pathophysiology of cardiovascular diseases, including atherosclerosis, hypertension, and myocardial ischemia-reperfusion injury. In this review, we summarize the roles of LOXs and their products in different cardiovascular cells and conditions, offering valuable insights may contribute to the development of novel therapeutic strategies for cardiovascular diseases.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"599-610"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heidi S Lumish, Lorenzo R Sewanan, Lusha W Liang, Kohei Hasegawa, Mathew S Maurer, Muredach P Reilly, Yuichi J Shimada
{"title":"Comprehensive Plasma Proteomic Profiling Reveals Differentially Regulated Signaling Pathways Underlying Left Ventricular Hypertrophy Between Hypertrophic Cardiomyopathy and Aortic Stenosis.","authors":"Heidi S Lumish, Lorenzo R Sewanan, Lusha W Liang, Kohei Hasegawa, Mathew S Maurer, Muredach P Reilly, Yuichi J Shimada","doi":"10.1007/s12265-025-10618-x","DOIUrl":"10.1007/s12265-025-10618-x","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is the most common genetic myocardial disease, characterized by asymmetric left ventricular hypertrophy (LVH) due to sarcomeric mutations. Aortic stenosis (AS) results in concentric LVH, due to pressure overload. The aim of this study was to identify signaling pathways differentially regulated in HCM compared to AS, using plasma proteomic profiling. 76 HCM cases and 36 AS controls were matched by age and sex. A machine-learning (ML) model to predict HCM was built in the training set (70% cohort) and examined in the test set (30% cohort). Pathway analysis of proteins differentially expressed between HCM and AS was performed. The ML model accurately distinguished HCM from AS, with area under the receiver operating characteristic curve of 0.90 (95% CI: 0.79-1.00). Pathway analysis revealed differential regulation of Ras-MAPK, inflammatory and metabolic pathways. In conclusion, this study identified distinctive proteomic profiles and signaling pathways underlying LVH in HCM compared to AS.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"650-659"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sensitivity of Left Atrial Flow Dynamics to Echocardiographic and Computed Tomography Data.","authors":"Ahmad Bshennaty, Brennan J Vogl, Ghasaq Saleh, Agata Sularz, Mohamad Alkhouli, Hoda Hatoum","doi":"10.1007/s12265-025-10598-y","DOIUrl":"10.1007/s12265-025-10598-y","url":null,"abstract":"<p><p>Computational simulations are a powerful tool in the understanding, diagnosing, and treatment of cardiovascular diseases. Incomplete clinical data often limits computational assessment, which may lead to inaccuracies. This study aims to assess the sensitivity of left atrial flow dynamics to echocardiographic and computed tomography data. Models of the LA were reconstructed at the E-wave(Geometry 1)and end-diastolic(Geometry 2)phases from CT scans. CFD simulations were carried out using 3 different sets of BCs. BC2 and BC3 presented similar results that were significantly different from BC1. The effect from the choice of geometry was significant with BC2 and BC3 but minor with BC1. Differences in parameters across the simulated cases highlight the importance of using consistent BCs and geometries for CFD studies. Acquiring the pressure in the LA does not seem to be necessary for the accuracy of CFD simulations. Validation of all simulations indicates reliable patient-specific results.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"689-701"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association Between Magnesium Depletion Score and Peripheral Artery Disease in Middle-Aged and Older Population.","authors":"Zongao Cai, Jiachen She","doi":"10.1007/s12265-025-10615-0","DOIUrl":"10.1007/s12265-025-10615-0","url":null,"abstract":"<p><p>The magnesium depletion score (MDS) is considered a new valuable predictor of body magnesium status. This study aimed to explore the association between MDS and PAD among participants aged ≥ 40 years on the National Health and Nutrition Examination Survey in 1999-2004. Survey-weighted multivariable logistic regression and restricted cubic spline models were used to assess the association between MDS and PAD. Survey-weighted multivariable logistic regression showed a significant positive association between MDS and the prevalence of PAD. For each unit increase in MDS, the risk of PAD increased by 24%. Compared to individuals with MDS = 0, those with MDS ≥ 3 had a 95% higher risk of PAD. Restricted triple spline analysis showed a linear dose-response relationship between MDS and PAD risk. Subgroup analysis indicated that this positive association was stronger in individuals aged > 60 years. Numerous future longitudinal cohort studies are required to validate our findings.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"624-633"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucas Su Chen, Gabriel Koh, Yak-Nam Wang, Ga Won Kim, Zorawar Singh, Adrienne Lehnert, Robert Miyaoka, Hitinder S Gurm, Adam D Maxwell
{"title":"Fracture and Fragmentation of Vascular Calcifications by Focused Ultrasound.","authors":"Lucas Su Chen, Gabriel Koh, Yak-Nam Wang, Ga Won Kim, Zorawar Singh, Adrienne Lehnert, Robert Miyaoka, Hitinder S Gurm, Adam D Maxwell","doi":"10.1007/s12265-025-10611-4","DOIUrl":"10.1007/s12265-025-10611-4","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"670-680"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evelyne Demkes, Aina Cervera-Barea, Patricia Ebner-Peking, Martin Wolf, Sarah Hochmann, Amy S Scheren, Mayke Bijsterveld, C Marlies van Oostveen, Marlijn Jansen, Joyce Visser, Wiebke Triebert, Caroline Halloin, Johannes G G Dobbe, Judith de Vos, Melanie Schürz, Joachim Danmayr, Maurice C G Aalders, Gerard J J Boink, Klaus Neef, Dirk Strunk, Robert Zweigerdt, Saskia C A de Jager, Joost P G Sluijter
{"title":"Human Cardiac Microtissues Display Improved Engraftment and Survival in a Porcine Model of Myocardial Infarction.","authors":"Evelyne Demkes, Aina Cervera-Barea, Patricia Ebner-Peking, Martin Wolf, Sarah Hochmann, Amy S Scheren, Mayke Bijsterveld, C Marlies van Oostveen, Marlijn Jansen, Joyce Visser, Wiebke Triebert, Caroline Halloin, Johannes G G Dobbe, Judith de Vos, Melanie Schürz, Joachim Danmayr, Maurice C G Aalders, Gerard J J Boink, Klaus Neef, Dirk Strunk, Robert Zweigerdt, Saskia C A de Jager, Joost P G Sluijter","doi":"10.1007/s12265-025-10596-0","DOIUrl":"10.1007/s12265-025-10596-0","url":null,"abstract":"<p><p>Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) constitute a promising therapy for myocardial infarction (MI). The lack of an effective immunosuppressive regimen, combined with single-cell transplantations, results in suboptimal outcomes, such as poor engraftment and compromised therapeutic efficacy. This study aimed to confirm the increased retention of hiPSC-CMs microtissues (CMTs) over single-cell grafts. To ensure the long-term survival of CMTs for potential cardiac applications, CMTs were transplanted in a porcine model of MI using a triple immunosuppression protocol designed to limit immune cell infiltration. Acute evaluation of spherical hiPSC-CMs aggregates and dissociated aggregates followed by the development of a triple immunosuppression protocol were performed in healthy animals. Long-term survival of CMTs was later examined in pigs that underwent a transient coronary occlusion. Two weeks post-MI, the immunosuppression treatment was initiated and on day 28 the animals were transplanted with CMTs and followed for four more weeks. Acutely, CMTs showed superior retention compared to their dissociated counterparts. The immunosuppression regimen led to no organ damage and stable levels of circulating drugs once optimal dose was achieved. Two weeks post-xenotransplantation in healthy pigs, histology revealed that immunosuppressed animals displayed a significant decrease in total cellular infiltrates, particularly in CD3<sup>+</sup> T cells. Pigs that underwent coronary occlusion, which later were immunosuppressed and treated with CMTs (5 × 10<sup>7</sup> cells), showed cell engraftment onto the native myocardium four weeks post-transplantation. This study supports the use of a triple immunosuppression cocktail to ensure long-term survival of CMTs for the treatment of MI.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"512-528"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of Mitophagy in Cardiac Metabolic Remodeling of Heart Failure: Insights of Molecular Mechanisms and Therapeutic Prospects.","authors":"Fangying Yan, Liwen Bao","doi":"10.1007/s12265-025-10606-1","DOIUrl":"10.1007/s12265-025-10606-1","url":null,"abstract":"<p><p>Heart failure (HF) treatment remains one of the major challenges in cardiovascular disease management, and its pathogenesis requires further exploration. Cardiac metabolic remodeling is of great significance as a key pathological process in the progression of HF. The complex alterations of metabolic substrates and associated enzymes in mitochondria create a vicious cycle in HF. These changes lead to increased reactive oxygen species, altered mitochondrial Ca<sup>2+</sup> handling, and the accumulation of fatty acids, contributing to impaired mitochondrial function. In this context, mitophagy plays a significant role in clearing damaged mitochondria, thereby maintaining mitochondrial function and preserving cardiac function by modulating metabolic remodeling in HF. This article aims to explore the role of mitophagy in cardiac metabolic remodeling in HF, especially in obesity cardiomyopathy, diabetic cardiomyopathy, and excessive afterload-induced heart failure, thoroughly analyze its molecular mechanisms, and review the therapeutic strategies and prospects based on the regulation of mitophagy.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"611-623"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alyssa R Thomas, Kristen Lazelle, Julia Garcia Mancebo, Padraic Romfh, John N Kheir
{"title":"Resonance Raman Spectroscopy Detects Ischemia in Experimental Coarctation of the Aorta in a Rodent Model.","authors":"Alyssa R Thomas, Kristen Lazelle, Julia Garcia Mancebo, Padraic Romfh, John N Kheir","doi":"10.1007/s12265-025-10599-x","DOIUrl":"10.1007/s12265-025-10599-x","url":null,"abstract":"<p><p>Coarctation of the aorta (CoA) can cause aortic obstruction, ischemia, and death. Resonance Raman Spectroscopy (RRS) measures tissue oxyhemoglobin (ShbO<sub>2</sub>) and mitochondrial redox state (3RMR) non-invasively. Metal wire was placed around the aorta of Sprague Dawley rats to generate a systolic blood pressure (SBP) gradient. RRS-ShbO<sub>2</sub> and 3RMR were measured pre- (hand) and post-obstruction (foot). In model 1 (n = 8), the gradient rapidly reached 120 mmHg. In model 2 (n = 30), gradients of 20 mmHg (n = 9) and 40 mmHg (n = 12) were maintained for 2 h. In model 1, foot-ShbO<sub>2</sub> and 3RMR changed significantly (P = 0.004 and P = 0.007) at SBP gradients of 80-mmHg or above. In model 2, the 40-mmHg gradient group showed significant declines in foot-ShbO2 (P = 0.014) and increases in 3RMR (P = 0.008) by 1 h. Foot-ShbO<sub>2</sub> and 3RMR correlated strongly with serum mixed venous saturation (ShbO<sub>2</sub>: r = 0.73, P < 0.0001; 3RMR: r = -0.55, P < 0.0001). RRS effectively detects ischemia caused by aortic obstruction in a CoA model.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"566-573"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Ding, Anqi Yang, Liping Zhou, Fulei Zhang, Huixing Zhou, Yuemei Zhang, Yan Wang, Yi Liu, Dandan Liang, Yuanyuan Liu, Yahan Wu
{"title":"PLK1 Downregulation Attenuates ET-1-Induced Cardiomyocyte Hypertrophy by Suppressing the ERK1/2 Pathway.","authors":"Jie Ding, Anqi Yang, Liping Zhou, Fulei Zhang, Huixing Zhou, Yuemei Zhang, Yan Wang, Yi Liu, Dandan Liang, Yuanyuan Liu, Yahan Wu","doi":"10.1007/s12265-025-10604-3","DOIUrl":"10.1007/s12265-025-10604-3","url":null,"abstract":"<p><p>Cardiomyocyte hypertrophy is a key remodeling response to cardiac stress and an independent risk factor for heart failure. However, the molecular mechanism of cardiomyocyte hypertrophy is not yet fully understood. We here found Polo-like kinase 1 (PLK1) was crucial in regulating endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy. Notably, PLK1 expression was significantly elevated in ET-1-induced hypertrophic cardiomyocytes and pressure overload-induced hypertrophic cardiac tissue. Knocking down Plk1 reduced the cell size of hypertrophic cardiomyocytes and suppressed the expression of hypertrophic markers, including ANP, BNP and β-MHC. The PLK1 inhibitor BI2536 had similar effects on hypertrophic cardiomyocytes. Mechanistically, the ERK1/2 pathway was identified as the key downstream pathway mediating the effects of PLK1 on ET-1-induced cardiomyocyte hypertrophy. Finally, the deficiency of PLK1 attenuated the hypertrophy of hiPSC-CMs. In summary, our study revealed that PLK1 regulates ET-1-induced cardiomyocyte hypertrophy through the ERK1/2 pathway, providing insights into the pathogenesis and potential therapies for pathological cardiac hypertrophy.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"586-598"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Clinical Significance of miR-139-5p in Acute Coronary Syndrome and its Potential Effect on the Progression of Acute Coronary Syndrome.","authors":"Zhe Wang, Qiaoli Ma, Fei Lin","doi":"10.1007/s12265-025-10625-y","DOIUrl":"https://doi.org/10.1007/s12265-025-10625-y","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}