Pub Date : 2024-04-01DOI: 10.1016/j.jacbts.2023.07.011
Margaret H. Hastings PhD , Claire Castro PhD , Rebecca Freeman BA , Azrul Abdul Kadir PhD , Carolin Lerchenmüller MD , Haobo Li PhD , James Rhee MD, PhD , Jason D. Roh MD, MHS , Kangsan Roh PhD , Anand P. Singh PhD , Chao Wu MD, PhD , Peng Xia PhD , Qiulian Zhou PhD , Junjie Xiao MD, PhD , Anthony Rosenzweig MD
Among its many cardiovascular benefits, exercise training improves heart function and protects the heart against age-related decline, pathological stress, and injury. Here, we focus on cardiac benefits with an emphasis on more recent updates to our understanding. While the cardiomyocyte continues to play a central role as both a target and effector of exercise’s benefits, there is a growing recognition of the important roles of other, noncardiomyocyte lineages and pathways, including some that lie outside the heart itself. We review what is known about mediators of exercise’s benefits—both those intrinsic to the heart (at the level of cardiomyocytes, fibroblasts, or vascular cells) and those that are systemic (including metabolism, inflammation, the microbiome, and aging)—highlighting what is known about the molecular mechanisms responsible.
{"title":"Intrinsic and Extrinsic Contributors to the Cardiac Benefits of Exercise","authors":"Margaret H. Hastings PhD , Claire Castro PhD , Rebecca Freeman BA , Azrul Abdul Kadir PhD , Carolin Lerchenmüller MD , Haobo Li PhD , James Rhee MD, PhD , Jason D. Roh MD, MHS , Kangsan Roh PhD , Anand P. Singh PhD , Chao Wu MD, PhD , Peng Xia PhD , Qiulian Zhou PhD , Junjie Xiao MD, PhD , Anthony Rosenzweig MD","doi":"10.1016/j.jacbts.2023.07.011","DOIUrl":"10.1016/j.jacbts.2023.07.011","url":null,"abstract":"<div><p>Among its many cardiovascular benefits, exercise training improves heart function and protects the heart against age-related decline, pathological stress, and injury. Here, we focus on cardiac benefits with an emphasis on more recent updates to our understanding. While the cardiomyocyte continues to play a central role as both a target and effector of exercise’s benefits, there is a growing recognition of the important roles of other, noncardiomyocyte lineages and pathways, including some that lie outside the heart itself. We review what is known about mediators of exercise’s benefits—both those intrinsic to the heart (at the level of cardiomyocytes, fibroblasts, or vascular cells) and those that are systemic (including metabolism, inflammation, the microbiome, and aging)—highlighting what is known about the molecular mechanisms responsible.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X23002942/pdfft?md5=48d166bf1f1061b3bc98170a1187c0e0&pid=1-s2.0-S2452302X23002942-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135848999","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 : 2024-04-01DOI: 10.1016/j.jacbts.2024.01.012
Jing Wang MM , Jie Chen MM , Ling Shu MM , Ruoliu Zhang MB , Mingyan Dai MD , Xuesheng Fang MB , Zhiling Hu MB , Lingling Xiao MB , Zhaoqing Xi MB , Junxia Zhang MD , Mingwei Bao MD
Autonomic nervous system imbalance is intricately associated with the severity and prognosis of pulmonary arterial hypertension (PAH). Carotid baroreceptor stimulation (CBS) is a nonpharmaceutical intervention for autonomic neuromodulation. The effects of CBS on monocrotaline-induced PAH were investigated in this study, and its underlying mechanisms were elucidated. The results indicated that CBS improved pulmonary hemodynamic status and alleviated right ventricular dysfunction, improving pulmonary arterial remodeling and right ventricular remodeling, thus enhancing the survival rate of monocrotaline-induced PAH rats. The beneficial effects of CBS treatment on PAH might be mediated through the inhibition of sympathetic overactivation and inflammatory immune signaling pathways.
自主神经系统失衡与肺动脉高压(PAH)的严重程度和预后密切相关。颈动脉气压感受器刺激(CBS)是一种非药物的自律神经调节干预方法。本研究探讨了 CBS 对单克罗林诱导的 PAH 的影响,并阐明了其潜在机制。结果表明,CBS能改善肺血流动力学状态,缓解右心室功能障碍,改善肺动脉重塑和右心室重塑,从而提高单克隆肾上腺素诱导的PAH大鼠的存活率。CBS治疗对PAH的有益作用可能是通过抑制交感神经过度激活和炎症免疫信号通路介导的。
{"title":"Carotid Baroreceptor Stimulation Improves Pulmonary Arterial Remodeling and Right Ventricular Dysfunction in Pulmonary Arterial Hypertension","authors":"Jing Wang MM , Jie Chen MM , Ling Shu MM , Ruoliu Zhang MB , Mingyan Dai MD , Xuesheng Fang MB , Zhiling Hu MB , Lingling Xiao MB , Zhaoqing Xi MB , Junxia Zhang MD , Mingwei Bao MD","doi":"10.1016/j.jacbts.2024.01.012","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.01.012","url":null,"abstract":"<div><p>Autonomic nervous system imbalance is intricately associated with the severity and prognosis of pulmonary arterial hypertension (PAH). Carotid baroreceptor stimulation (CBS) is a nonpharmaceutical intervention for autonomic neuromodulation. The effects of CBS on monocrotaline-induced PAH were investigated in this study, and its underlying mechanisms were elucidated. The results indicated that CBS improved pulmonary hemodynamic status and alleviated right ventricular dysfunction, improving pulmonary arterial remodeling and right ventricular remodeling, thus enhancing the survival rate of monocrotaline-induced PAH rats. The beneficial effects of CBS treatment on PAH might be mediated through the inhibition of sympathetic overactivation and inflammatory immune signaling pathways.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X2400041X/pdfft?md5=998f48ef8365f3b6ee9c3a2cdfdc1acb&pid=1-s2.0-S2452302X2400041X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140638640","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 : 2024-04-01DOI: 10.1016/j.jacbts.2024.01.007
Hugo Alves-Figueiredo PhD , Christian Silva-Platas PhD , Manuel Estrada PhD , Yuriana Oropeza-Almazán PhD , Martin Ramos-González MD, PhD , Judith Bernal-Ramírez PhD , Eduardo Vázquez-Garza MD, PhD , Armando Tellez PhD , Felipe Salazar-Ramírez MD, MSc , Abraham Méndez-Fernández MSc , José Luis Galaz MD , Pedro Lobos PhD , Keith Youker PhD , Omar Lozano PhD , Guillermo Torre-Amione MD, PhD , Gerardo García-Rivas PhD
The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)–induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B–dependent hypertrophic and proinflammatory signaling. Moreover, we identified a calcium/calmodulin–independent protein kinase II/cyclic adenosine monophosphate response element–binding protein signaling modulating MCU upregulation by ANGII. Additionally, we found upregulation of MCU in ANGII-induced left ventricular HF in mice, and in the LV of HF patients, which was correlated with pathological remodeling. Following left ventricular assist device implantation, MCU expression decreased, suggesting tissue plasticity to modulate MCU expression.
{"title":"Mitochondrial Ca2+ Uniporter–Dependent Energetic Dysfunction Drives Hypertrophy in Heart Failure","authors":"Hugo Alves-Figueiredo PhD , Christian Silva-Platas PhD , Manuel Estrada PhD , Yuriana Oropeza-Almazán PhD , Martin Ramos-González MD, PhD , Judith Bernal-Ramírez PhD , Eduardo Vázquez-Garza MD, PhD , Armando Tellez PhD , Felipe Salazar-Ramírez MD, MSc , Abraham Méndez-Fernández MSc , José Luis Galaz MD , Pedro Lobos PhD , Keith Youker PhD , Omar Lozano PhD , Guillermo Torre-Amione MD, PhD , Gerardo García-Rivas PhD","doi":"10.1016/j.jacbts.2024.01.007","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.01.007","url":null,"abstract":"<div><p>The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)–induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B–dependent hypertrophic and proinflammatory signaling. Moreover, we identified a calcium/calmodulin–independent protein kinase II/cyclic adenosine monophosphate response element–binding protein signaling modulating MCU upregulation by ANGII. Additionally, we found upregulation of MCU in ANGII-induced left ventricular HF in mice, and in the LV of HF patients, which was correlated with pathological remodeling. Following left ventricular assist device implantation, MCU expression decreased, suggesting tissue plasticity to modulate MCU expression.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000111/pdfft?md5=33f5014a0200ad9d38463fc1925dcf56&pid=1-s2.0-S2452302X24000111-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140638642","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}
The role of atrial metabolism alterations for initiation and atrial fibrillation (AF) persistence remains poorly understood. Therefore, we evaluated left atrial glucose metabolism by nicotinic acid derivative stimulated 18-fluorodeoxyglucose positron emission tomography in 36 patients with persistent AF undergoing catheter ablation before and 3 months after return to sinus rhythm and compared values against healthy controls. Under identical hemodynamics and metabolic conditions, and although left ventricular FDG uptake remained unchanged, patients in persistent AF presented significantly higher total left atrial and left atrial appendage uptake, which decreased significantly after return to sinus rhythm, despite improvement of passive and active atrial contractile function. These findings support a role of altered glucose metabolism and metabolic wasting underlying the pathophysiology of persistent AF.
{"title":"Left Atrial Glucose Metabolism Evaluation by 18F-FDG-PET in Persistent Atrial Fibrillation and in Sinus Rhythm","authors":"Sébastien Marchandise MD , Véronique Roelants MD, PhD , Tristan Raoult MD , Quentin Garnir MD , Christophe Scavée MD , Varnavas Varnavas MD PhD , Aurélien Wauters MD, PhD , Damien Gruson MD, PhD , Eric Nellessen MD , Michel Hesse PhD , Christophe Beauloye MD, PhD , Bernhard L. Gerber MD, PhD","doi":"10.1016/j.jacbts.2023.11.001","DOIUrl":"10.1016/j.jacbts.2023.11.001","url":null,"abstract":"<div><p>The role of atrial metabolism alterations for initiation and atrial fibrillation (AF) persistence remains poorly understood. Therefore, we evaluated left atrial glucose metabolism by nicotinic acid derivative stimulated 18-fluorodeoxyglucose positron emission tomography in 36 patients with persistent AF undergoing catheter ablation before and 3 months after return to sinus rhythm and compared values against healthy controls. Under identical hemodynamics and metabolic conditions, and although left ventricular FDG uptake remained unchanged, patients in persistent AF presented significantly higher total left atrial and left atrial appendage uptake, which decreased significantly after return to sinus rhythm, despite improvement of passive and active atrial contractile function. These findings support a role of altered glucose metabolism and metabolic wasting underlying the pathophysiology of persistent AF.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X23005132/pdfft?md5=ba19dd4a2189016bb341b4eccfdb8337&pid=1-s2.0-S2452302X23005132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509842","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 : 2024-04-01DOI: 10.1016/j.jacbts.2024.02.018
Natalie M. Niemi PhD
{"title":"Mitochondrial Calcium Flux—Friend or Foe in Chronic Heart Failure?∗","authors":"Natalie M. Niemi PhD","doi":"10.1016/j.jacbts.2024.02.018","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.02.018","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000974/pdfft?md5=46390f1d2a093731402ea4392fcde236&pid=1-s2.0-S2452302X24000974-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140638492","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 : 2024-04-01DOI: 10.1016/j.jacbts.2024.04.004
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.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.04.004","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001426/pdfft?md5=544c4db770b66b262e00fa69e7f11f20&pid=1-s2.0-S2452302X24001426-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140880237","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}