Pub Date : 2025-01-01DOI: 10.1016/j.jacbts.2024.09.004
Florence M. Herisson PhD , Gaston L. Cluzel PhD , Maria Antonia Llopis-Grimalt PhD , Aoife N. O’Donovan PhD , Fatma Koc PhD , Kavita Karnik PhD , Ieva Laurie PhD , Kirstie Canene-Adams PhD , R. Paul Ross PhD , Catherine Stanton PhD , Noel M. Caplice MD, PhD
Poor diet, gut dysbiosis, and systemic inflammation constitute a gut-heart axis (GHA) that may affect heart failure with preserved ejection fraction. Clinical scale models to interrogate this axis are limited. Here, we show the full extent of the GHA–gut barrier function loss, systemic and microvascular inflammation, and its colocalization with apoptosis (left atrium) and hypertrophy (left ventricle). Gut barrier function primacy in regulating the GHA is supported by a synbiotic intervention that shuts down gut epithelial permeability, markedly decreasing systemic inflammation and, remarkably, cardiac structural changes in left heart chambers. These data support a new paradigm for targeting heart failure with preserved ejection fraction via the GHA.
{"title":"Targeting the Gut-Heart Axis Improves Cardiac Remodeling in a Clinical Scale Model of Cardiometabolic Syndrome","authors":"Florence M. Herisson PhD , Gaston L. Cluzel PhD , Maria Antonia Llopis-Grimalt PhD , Aoife N. O’Donovan PhD , Fatma Koc PhD , Kavita Karnik PhD , Ieva Laurie PhD , Kirstie Canene-Adams PhD , R. Paul Ross PhD , Catherine Stanton PhD , Noel M. Caplice MD, PhD","doi":"10.1016/j.jacbts.2024.09.004","DOIUrl":"10.1016/j.jacbts.2024.09.004","url":null,"abstract":"<div><div>Poor diet, gut dysbiosis, and systemic inflammation constitute a gut-heart axis (GHA) that may affect heart failure with preserved ejection fraction. Clinical scale models to interrogate this axis are limited. Here, we show the full extent of the GHA–gut barrier function loss, systemic and microvascular inflammation, and its colocalization with apoptosis (left atrium) and hypertrophy (left ventricle). Gut barrier function primacy in regulating the GHA is supported by a synbiotic intervention that shuts down gut epithelial permeability, markedly decreasing systemic inflammation and, remarkably, cardiac structural changes in left heart chambers. These data support a new paradigm for targeting heart failure with preserved ejection fraction via the GHA.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 1","pages":"Pages 1-15"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jacbts.2024.08.011
Victoria R. Palzkill BS , Jianna Tan BS , Divyansha Moparthy , Abigail L. Tice PhD , Leonardo F. Ferreira PhD , Terence E. Ryan PhD
In this study, we present a novel 6-minute limb function test that allows for the congruent assessment of muscular performance and hemodynamics in preclinical models of peripheral artery disease. Using several experimental conditions, the results demonstrate the superior efficacy of the 6-minute limb function test to detect differences in the response to hindlimb ischemia across several interventions, including where traditional perfusion recovery, capillary density, and muscle strength measures were unable to detect interventional differences, thus allowing for more rigorous assessment of preclinical therapies before clinical translation.
{"title":"A 6-Minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models","authors":"Victoria R. Palzkill BS , Jianna Tan BS , Divyansha Moparthy , Abigail L. Tice PhD , Leonardo F. Ferreira PhD , Terence E. Ryan PhD","doi":"10.1016/j.jacbts.2024.08.011","DOIUrl":"10.1016/j.jacbts.2024.08.011","url":null,"abstract":"<div><div>In this study, we present a novel 6-minute limb function test that allows for the congruent assessment of muscular performance and hemodynamics in preclinical models of peripheral artery disease. Using several experimental conditions, the results demonstrate the superior efficacy of the 6-minute limb function test to detect differences in the response to hindlimb ischemia across several interventions, including where traditional perfusion recovery, capillary density, and muscle strength measures were unable to detect interventional differences, thus allowing for more rigorous assessment of preclinical therapies before clinical translation.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 1","pages":"Pages 88-103"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As major noncardiomyocyte components in cardiac tissues, macrophages and fibroblasts play crucial roles in maintaining cardiac homeostasis, orchestrating reparative responses after cardiac injuries, facilitating adaptive cardiac remodeling, and contributing to adverse cardiac remodeling, owing to their inherent heterogeneity and plasticity. Recent advances in research methods have yielded novel insights into the intricate interactions between macrophages and fibroblasts in the cardiac context. This review aims to comprehensively examine the molecular mechanisms governing macrophage-fibroblast interactions in cardiac homeostasis and remodeling, emphasize recent advancements in the field, and offer an evaluation from a translational standpoint.
{"title":"Emerging Role of Macrophage-Fibroblast Interactions in Cardiac Homeostasis and Remodeling","authors":"Xu-Zhe Zhang MD , Qin-Lin Li MB , Ting-Ting Tang MD, PhD , Xiang Cheng MD, PhD","doi":"10.1016/j.jacbts.2024.06.003","DOIUrl":"10.1016/j.jacbts.2024.06.003","url":null,"abstract":"<div><div>As major noncardiomyocyte components in cardiac tissues, macrophages and fibroblasts play crucial roles in maintaining cardiac homeostasis, orchestrating reparative responses after cardiac injuries, facilitating adaptive cardiac remodeling, and contributing to adverse cardiac remodeling, owing to their inherent heterogeneity and plasticity. Recent advances in research methods have yielded novel insights into the intricate interactions between macrophages and fibroblasts in the cardiac context. This review aims to comprehensively examine the molecular mechanisms governing macrophage-fibroblast interactions in cardiac homeostasis and remodeling, emphasize recent advancements in the field, and offer an evaluation from a translational standpoint.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 1","pages":"Pages 113-127"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142207142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jacbts.2024.09.007
Marta Brambilla PhD , Federica Fumoso MD , Maria Conti MS , Alessia Becchetti MS , Silvia Bozzi PhD , Tatiana Mencarini PhD , Piergiuseppe Agostoni MD, PhD , Maria E. Mancini MD , Nicola Cosentino MD, PhD , Alice Bonomi PhD , Kevin Nallio MS , Arianna Galotta MS , Martino Pengo MD, PhD , Elena Tortorici MD , Miriam Bosco MD , Franco Cernigliaro MD , Chistian Pinna PhD , Daniele Andreini MD, PhD , Marina Camera PhD
In the present study, we provide evidence on the potential mechanisms involved in the residual pulmonary impairment described in long COVID syndrome. Data highlight that lung damage is significantly associated with a proinflammatory platelet phenotype, characterized mainly by the formation of platelet-leukocyte aggregates. In ex vivo experiments, long COVID plasma reproduces the platelet activation observed in vivo and highlights low-grade inflammation as a potential underpinning mechanism, exploiting a synergistic activity between C-reactive protein and subthreshold concentrations of interleukin-6. The platelet-activated phenotype is blunted by anti-inflammatory and antiplatelet drugs, suggesting a potential therapeutic option in this clinical setting.
{"title":"Low-Grade Inflammation in Long COVID Syndrome Sustains a Persistent Platelet Activation Associated With Lung Impairment","authors":"Marta Brambilla PhD , Federica Fumoso MD , Maria Conti MS , Alessia Becchetti MS , Silvia Bozzi PhD , Tatiana Mencarini PhD , Piergiuseppe Agostoni MD, PhD , Maria E. Mancini MD , Nicola Cosentino MD, PhD , Alice Bonomi PhD , Kevin Nallio MS , Arianna Galotta MS , Martino Pengo MD, PhD , Elena Tortorici MD , Miriam Bosco MD , Franco Cernigliaro MD , Chistian Pinna PhD , Daniele Andreini MD, PhD , Marina Camera PhD","doi":"10.1016/j.jacbts.2024.09.007","DOIUrl":"10.1016/j.jacbts.2024.09.007","url":null,"abstract":"<div><div>In the present study, we provide evidence on the potential mechanisms involved in the residual pulmonary impairment described in long COVID syndrome. Data highlight that lung damage is significantly associated with a proinflammatory platelet phenotype, characterized mainly by the formation of platelet-leukocyte aggregates. In ex vivo experiments, long COVID plasma reproduces the platelet activation observed in vivo and highlights low-grade inflammation as a potential underpinning mechanism, exploiting a synergistic activity between C-reactive protein and subthreshold concentrations of interleukin-6. The platelet-activated phenotype is blunted by anti-inflammatory and antiplatelet drugs, suggesting a potential therapeutic option in this clinical setting.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 1","pages":"Pages 20-39"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jacbts.2024.11.013
Harvey G. Roweth PhD
{"title":"The Lung and Winding Road","authors":"Harvey G. Roweth PhD","doi":"10.1016/j.jacbts.2024.11.013","DOIUrl":"10.1016/j.jacbts.2024.11.013","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 1","pages":"Pages 40-42"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jacbts.2024.12.002
Douglas L. Mann MD (Editor-in-Chief: JACC: Basic to Translational Science)
{"title":"Recognizing Early Career Translational Investigators","authors":"Douglas L. Mann MD (Editor-in-Chief: JACC: Basic to Translational Science)","doi":"10.1016/j.jacbts.2024.12.002","DOIUrl":"10.1016/j.jacbts.2024.12.002","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 1","pages":"Page 128"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jacbts.2024.12.001
Brian H. Annex MD, Michael R. Bristow MD, PhD, Nikolaus G. Frangogiannis MD, Daniel P. Kelly MD, Maria Kontaridis PhD, Peter Libby MD, William Robb MacLellan MD, Coleen A. McNamara MD, Douglas L. Mann MD, Geoffrey S. Pitt MD, PhD, Karin R. Sipido MD, PhD
{"title":"JACC: Basic to Translational Science","authors":"Brian H. Annex MD, Michael R. Bristow MD, PhD, Nikolaus G. Frangogiannis MD, Daniel P. Kelly MD, Maria Kontaridis PhD, Peter Libby MD, William Robb MacLellan MD, Coleen A. McNamara MD, Douglas L. Mann MD, Geoffrey S. Pitt MD, PhD, Karin R. Sipido MD, PhD","doi":"10.1016/j.jacbts.2024.12.001","DOIUrl":"10.1016/j.jacbts.2024.12.001","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 1","pages":"Page 129"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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