Cardiovascular Research最新文献

{"title":"Integrated proteomics identifies troponin I isoform switch as a regulator of a sarcomere-metabolism axis during cardiac regeneration","authors":"Timothy J Aballo, Jiyoung Bae, Wyatt G Paltzer, Emily A Chapman, Andrew J Perciaccante, Melissa R Pergande, Rebecca J Salamon, Dakota J Nuttall, Morgan W Mann, Ying Ge, Ahmed I Mahmoud","doi":"10.1093/cvr/cvaf069","DOIUrl":"https://doi.org/10.1093/cvr/cvaf069","url":null,"abstract":"Aims Adult mammalian cardiomyocytes have limited regenerative potential, and after myocardial infarction (MI), injured cardiac tissue is replaced with fibrotic scar. In contrast, the neonatal mouse heart possesses a regenerative capacity governed by cardiomyocyte proliferation; however, a metabolic switch from glycolysis to fatty acid oxidation during postnatal development results in loss of this regenerative capacity. Interestingly, a sarcomere isoform switch also takes place during postnatal development where slow skeletal troponin I (ssTnI) is replaced with cardiac troponin I (cTnI). It remains unclear whether there is an interplay between sarcomere isoform switching, cardiac metabolism, and regeneration. Methods and results In this study, we employ proteomics, metabolomics and lipidomics, transgenic mice, MI models, and histological analysis to delineate the molecular and sarcomeric transitions that occur during cardiac maturation and regeneration. First, we utilize integrated quantitative bottom-up and top-down proteomics to comprehensively define the proteomic and sarcomeric landscape during postnatal heart maturation. By employing a cardiomyocyte-specific ssTnI transgenic mouse model, we discovered that ssTnI overexpression increased cardiomyocyte proliferation and the cardiac regenerative capacity of the postnatal heart following MI compared to control mice by histological analysis. Our global proteomic analysis of ssTnI transgenic mice following MI reveals that ssTnI overexpression induces a significant shift in the cardiac proteomic landscape. Additionally, our lipidomic analysis demonstrated a significant upregulation of lipid species in the transgenic mice. This proteomic shift is characterized by an upregulation of key proteins involved in glycolytic metabolism. Conclusions Collectively, our data suggest that the postnatal TnI isoform switch may play a role in the metabolic shift from glycolysis to fatty acid oxidation during postnatal maturation. This underscores the significance of a sarcomere-metabolism axis during cardiomyocyte proliferation and heart regeneration.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"23 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced intracranial aneurysm development in a rat model of polycystic kidney disease","authors":"Anne F Cayron, Sandrine Morel, Maral Azam, Julien Haemmerli, Tomohiro Aoki, Philippe Bijlenga, Eric Allémann, Brenda R Kwak","doi":"10.1093/cvr/cvaf063","DOIUrl":"https://doi.org/10.1093/cvr/cvaf063","url":null,"abstract":"Aim Polycystic kidney disease (PKD) patients have a high intracranial aneurysms (IAs) incidence and risk of rupture. The mechanisms that make PKD patients more vulnerable to IA disease are still not completely understood. The PCK rat is a well-known PKD model and has been extensively used to study cyst development and kidney damage. Here, we used this rat model to study IA induction and vulnerability. Methods and results IAs were induced in wild-type (WT) and PCK rats and their incidence was followed. Variation in the anatomy of the circle of Willis was studied in PCK rats and PKD patients. Immunohistochemistry was performed in rat IAs and in human ruptured and unruptured IAs from patients enrolled in the @neurIST observational cohort. An increased frequency of fatal aortic dissection was unexpectedly observed in PCK rats, which was due to modifications in the elastic architecture of the aorta in combination with the induced hypertension. Interestingly, IAs developed faster in PCK rats compared to WT rats. Variations in the anatomy of the circle of Willis were identified in PCK rats and PKD patients, a risk factor that may (in part) explain the higher IA incidence found in these groups. At 2-weeks after induction, the endothelium of IAs from PCK rats showed a decrease in the tight junction proteins zonula occludens-1 and claudin-5. Furthermore, the type III collagen content was lower in IAs of PCK rats at 4-weeks post-surgery. The decrease in tight junction proteins was also observed in the endothelium of human ruptured IAs compared to unruptured IAs. Conclusions Our study showed that PCK rats are more sensitive to IA induction. Variations in the anatomy of the circle of Willis and impaired regulation of tight junction proteins might put PCK rats and PKD patients more at risk of developing vulnerable IAs.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"43 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It's all c-Relative. A new perspective for a member of the NF-κB family.","authors":"Jonathan O'Connor-Miranda,Anthony Parent,Stephanie Lehoux","doi":"10.1093/cvr/cvaf053","DOIUrl":"https://doi.org/10.1093/cvr/cvaf053","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"17 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined circulating microRNA and peptide biomarkers for prognostication in heart failure.","authors":"Lee Lee Wong,Hiromi W L Koh,Hyungwon Choi,Ruiyang Zou,Lihan Zhou,Jia Yuen Lim,Dominic C Y Phua,Oi Wah Liew,Jenny P C Chong,Jessica Y X Ng,Siew Pang Chan,Yei-Tsung Chen,Poh Shuan D Yeo,Lieng H Ling,David Sim,Kui Toh G Leong,Hean Y Ong,Fazlur Jaufeerally,Raymond Wong,Ping Chai,Adrian F Low,Mayanna Lund,Gerry Devlin,Richard Troughton,Robert N Doughty,Carolyn S P Lam,Heng Phon Too,Arthur Mark Richards","doi":"10.1093/cvr/cvaf065","DOIUrl":"https://doi.org/10.1093/cvr/cvaf065","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"44 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tiny trouble: microplastics, nanoplastics, and their heartfelt impact on cardiovascular health","authors":"Tongyao Zhang, Yajie Liao, Jitao Ling, Jing Zhang, Deju Zhang, Xiaoping Yin, Peng Yu, Xiao Liu","doi":"10.1093/cvr/cvaf068","DOIUrl":"https://doi.org/10.1093/cvr/cvaf068","url":null,"abstract":"Microplastics and nanoplastics are ubiquitous environmental pollutants that pose significant health risks. Several studies have reported the presence of these particles in various human tissues, including the heart, arterial plaques, and bloodstream of patients undergoing percutaneous coronary interventions. Emerging research suggests an association between these particles and an increased risk of cardiovascular diseases. In vitro and in vivo studies reveal that micro- and nanoplastics induce endothelial cell toxicity, disrupt lipid metabolism, promote oxidative stress, and facilitate foam cell formation, thereby exacerbating atherosclerosis. Furthermore, they activate inflammatory pathways, compromising vascular barrier integrity. These particles also influence coagulation dynamics by altering clotting cascade activation and promoting thrombus formation. Additionally, they induce hemolysis, alter red blood cell morphology, and impair immune cell functions, including those of macrophages and lymphocytes, by modulating cytokine secretion and inflammatory responses. Understanding these mechanisms is essential for devising effective public health strategies to mitigate the cardiovascular impact of micro- and nanoplastics.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"27 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revivifying research on relaxin receptor-targeted therapy for cardiovascular diseases.","authors":"Xiao-Jun Du","doi":"10.1093/cvr/cvaf057","DOIUrl":"https://doi.org/10.1093/cvr/cvaf057","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"7 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of MRAP2 in MC4R neurons protect from obesity-associated autonomic and cardiovascular dysfunctions","authors":"Deng Fu Guo, Paul A Williams, Alexis Olson, Donald A Morgan, Hussein Herz, Jon Resch, Deniz Atasoy, Harald M Stauss, Julien A Sebag, Kamal Rahmouni","doi":"10.1093/cvr/cvaf067","DOIUrl":"https://doi.org/10.1093/cvr/cvaf067","url":null,"abstract":"Aims The melanocortin receptor accessory protein 2 (MRAP2), which is abundantly expressed in the brain including the hypothalamus, has emerged as a key regulator of melanocortin-4 receptor (MC4R) activity. We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on autonomic and cardiovascular functions. Methods and Results Selective deletion of MRAP2 in MC4R neurons causes obesity that was associated with hyperphagia and impairment in glucose homeostasis and insulin sensitivity. MC4R agonist Melatonan II (MTII)-induced anorectic effects were blunted in mice lacking MRAP2 in MC4R neurons, whereas Celastrol retained its efficacy in reducing food intake and body weight. MRAP2 deletion also reduced baseline sympathetic nerve activity (SNA), particularly the SNA subserving the kidney. This was associated with reduced innervation of the kidney. In addition, MTII-induced increases in renal and brown adipose tissue (BAT) SNA as well as hepatic vagal nerve activity were significantly attenuated in MC4R neuron MRAP2-deficient mice. Anatomical tracing revealed that MC4R neurons projecting to BAT and kidneys were localized to specific brain nuclei including the paraventricular nucleus of the hypothalamus, providing anatomical substrate for MRAP2 regulation of sympathetic outflow. Although loss of MRAP2 in MC4R neurons did not affect arterial pressure, it caused a significant decrease in heart rate and baroreflex sensitivity. Finally, MRAP2 deficiency in MC4R neurons attenuated MTII-induced increase in arterial pressure and heart rate. Conclusion These findings demonstrate that in addition to its role in energy balance and glucose homeostasis MRAP2 in MC4R neurons is crucial for cardiovascular autonomic regulation and is required for the development of obesity-associated hypertension and autonomic dysfunction.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"108 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinning the web of platelet tetraspanins under stress.","authors":"Madhumita Chatterjee","doi":"10.1093/cvr/cvaf062","DOIUrl":"https://doi.org/10.1093/cvr/cvaf062","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"18 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of epicardial adipose tissue remodelling in heart failure with preserved ejection fraction","authors":"Carolina Janssen-Telders, Etto C Eringa, Joris R de Groot, Frances S de Man, M Louis Handoko","doi":"10.1093/cvr/cvaf056","DOIUrl":"https://doi.org/10.1093/cvr/cvaf056","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) is a growing global health problem characterized by high morbidity and mortality, with limited effective therapies available. Obesity significantly influences haemodynamic and structural changes in the myocardium and vasculature, primarily through the accumulation and action of visceral adipose tissue. Particularly, epicardial adipose tissue (EAT) contributes to HFpEF through inflammation and lipotoxic infiltration of the myocardium. However, the precise signalling pathways leading to diastolic stiffness in HFpEF require further elucidation. This review explores the dynamic role of EAT in health and disease. Drawing upon insights from studies in other conditions, we discuss potential EAT-mediated inflammatory pathways in HFpEF and how they may contribute to functional and structural myocardial and endothelial derangements, including intramyocardial lipid infiltration, fibrosis, endothelial dysfunction, cardiomyocyte stiffening, and left ventricular hypertrophy. Lastly, we propose potential targets for novel therapeutic avenues.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"29 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta 2 adrenergic receptor gene methylation activates innate lymphoid cells to drive hypertension in lymphocyte deficient hosts.","authors":"Wei Chen,Sara Perrotta,Liang Xiao,Lorenzo Carnevale,Marwa A Abd-ElDayem,Elizabeth M Hennen,Luis Miguel Rivera-Medina,David M Patrick,Mingfang Ao,Fabio Pallante,Azzurra Zonfrilli,Shilin Zhao,Agnese Migliaccio,Lan Lan,Stefania Fardella,Giuseppe Sciumè,Francesco Mastroiacovo,Giuseppe Lembo,Daniela Carnevale,David G Harrison","doi":"10.1093/cvr/cvaf042","DOIUrl":"https://doi.org/10.1093/cvr/cvaf042","url":null,"abstract":"AIMST cells contribute to hypertension; however, hypertension occurs in settings of T cell deficiency.METHODS AND RESULTSWe studied two colonies of T/B cell-deficient RAG-1-/- mice with disparate responses to angiotensin II, being one protected from blood pressure increase and the other one responsive. This difference depends on the capability of hypertensive RAG-1-/- mice to expand natural killer and innate lymphoid cells (NK/ILCs) that produce pro-hypertensive cytokines. This process is regulated by the DNA methylation status of the β2 adrenergic receptor (β2-AdR). Angiotensin II caused blood pressure elevation in T and NK/ILCs-deficient mice only when either T or NK/ILCs cells were adoptively reconstituted. Additional studies showed NK cell expansion in humans that underwent B cell depletion, and this was augmented in those with hypertension.CONCLUSIONSThese findings illustrate that the modulation of NK/ILCs activation by adrenergic signalling governs an escape mechanism in lymphocyte-deficient host, enabling the development of hypertension.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"183 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}