Pub Date : 2024-05-01DOI: 10.1016/j.jacbts.2024.02.007
Anish Karpurapu BS , Helen A. Williams BS , Paige DeBenedittis PhD , Caroline E. Baker BS , Simiao Ren PhD , Michael C. Thomas BS , Anneka J. Beard MS , Garth W. Devlin BS , Josephine Harrington MD , Lauren E. Parker BS , Abigail K. Smith , Boyla Mainsah PhD , Michelle Mendiola Pla MD , Aravind Asokan PhD , Dawn E. Bowles PhD , Edwin Iversen PhD , Leslie Collins PhD , Ravi Karra MD, MHS
The adult mammalian heart harbors minute levels of cycling cardiomyocytes (CMs). Large numbers of images are needed to accurately quantify cycling events using microscopy-based methods. CardioCount is a new deep learning–based pipeline to rigorously score nuclei in microscopic images. When applied to a repository of 368,434 human microscopic images, we found evidence of coupled growth between CMs and cardiac endothelial cells in the adult human heart. Additionally, we found that vascular rarefaction and CM hypertrophy are interrelated in end-stage heart failure. CardioCount is available for use via GitHub and via Google Colab for users with minimal machine learning experience.
成年哺乳动物心脏中含有微量的循环心肌细胞(CMs)。使用基于显微镜的方法准确量化循环事件需要大量图像。CardioCount 是一种基于深度学习的新管道,可对显微图像中的细胞核进行严格评分。当应用于一个包含 368,434 幅人体显微图像的存储库时,我们发现了成人心脏中 CM 与心脏内皮细胞之间耦合生长的证据。此外,我们还发现在终末期心力衰竭中,血管稀疏和CM肥大是相互关联的。CardioCount 可通过 GitHub 使用,也可通过 Google Colab 提供给只有少量机器学习经验的用户使用。
{"title":"Deep Learning Resolves Myovascular Dynamics in the Failing Human Heart","authors":"Anish Karpurapu BS , Helen A. Williams BS , Paige DeBenedittis PhD , Caroline E. Baker BS , Simiao Ren PhD , Michael C. Thomas BS , Anneka J. Beard MS , Garth W. Devlin BS , Josephine Harrington MD , Lauren E. Parker BS , Abigail K. Smith , Boyla Mainsah PhD , Michelle Mendiola Pla MD , Aravind Asokan PhD , Dawn E. Bowles PhD , Edwin Iversen PhD , Leslie Collins PhD , Ravi Karra MD, MHS","doi":"10.1016/j.jacbts.2024.02.007","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.02.007","url":null,"abstract":"<div><p>The adult mammalian heart harbors minute levels of cycling cardiomyocytes (CMs). Large numbers of images are needed to accurately quantify cycling events using microscopy-based methods. CardioCount is a new deep learning–based pipeline to rigorously score nuclei in microscopic images. When applied to a repository of 368,434 human microscopic images, we found evidence of coupled growth between CMs and cardiac endothelial cells in the adult human heart. Additionally, we found that vascular rarefaction and CM hypertrophy are interrelated in end-stage heart failure. CardioCount is available for use via GitHub and via Google Colab for users with minimal machine learning experience.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000548/pdfft?md5=978db936761ec0f6df1d5fdff07202dc&pid=1-s2.0-S2452302X24000548-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141241292","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 : 2024-05-01DOI: 10.1016/j.jacbts.2023.10.007
Henry W. West BMedSci, MBBS, PhD , Katerina Dangas BA , Charalambos Antoniades MD, PhD
Vascular inflammation is a major contributor to cardiovascular disease, particularly atherosclerotic disease, and early detection of vascular inflammation may be key to the ultimate reduction of residual cardiovascular morbidity and mortality. This review paper discusses the progress toward the clinical utility of noninvasive imaging techniques for assessing vascular inflammation, with a focus on coronary atherosclerosis. A discussion of multiple modalities is included: computed tomography (CT) imaging (the major focus of the review), cardiac magnetic resonance, ultrasound, and positron emission tomography imaging. The review covers recent progress in new technologies such as the novel CT biomarkers of coronary inflammation (eg, the perivascular fat attenuation index), new inflammation-specific tracers for positron emission tomography–CT imaging, and others. The strengths and limitations of each modality are explored, highlighting the potential for multi-modality imaging and the use of artificial intelligence image interpretation to improve both diagnostic and prognostic potential for common conditions such as coronary artery disease.
{"title":"Advances in Clinical Imaging of Vascular Inflammation","authors":"Henry W. West BMedSci, MBBS, PhD , Katerina Dangas BA , Charalambos Antoniades MD, PhD","doi":"10.1016/j.jacbts.2023.10.007","DOIUrl":"10.1016/j.jacbts.2023.10.007","url":null,"abstract":"<div><p>Vascular inflammation is a major contributor to cardiovascular disease, particularly atherosclerotic disease, and early detection of vascular inflammation may be key to the ultimate reduction of residual cardiovascular morbidity and mortality. This review paper discusses the progress toward the clinical utility of noninvasive imaging techniques for assessing vascular inflammation, with a focus on coronary atherosclerosis. A discussion of multiple modalities is included: computed tomography (CT) imaging (the major focus of the review), cardiac magnetic resonance, ultrasound, and positron emission tomography imaging. The review covers recent progress in new technologies such as the novel CT biomarkers of coronary inflammation (eg, the perivascular fat attenuation index), new inflammation-specific tracers for positron emission tomography–CT imaging, and others. The strengths and limitations of each modality are explored, highlighting the potential for multi-modality imaging and the use of artificial intelligence image interpretation to improve both diagnostic and prognostic potential for common conditions such as coronary artery disease.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X23004643/pdfft?md5=148dcf2964c24edaf141033b19dfd39e&pid=1-s2.0-S2452302X23004643-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138691496","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 : 2024-05-01DOI: 10.1016/j.jacbts.2024.03.005
Olivier Morel MD, PhD
{"title":"Potential of Epigenetic Therapy in Alleviating Cardiac Death and Fibrotic Remodeling in Myocardial Infarction∗","authors":"Olivier Morel MD, PhD","doi":"10.1016/j.jacbts.2024.03.005","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.03.005","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001025/pdfft?md5=b2158699ad00555e347f75fe684ae985&pid=1-s2.0-S2452302X24001025-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141241286","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 : 2024-05-01DOI: 10.1016/j.jacbts.2024.02.019
Ruoyu Wang MM , Yue Zeng MM , Ziqi Chen PhD , Dongwei Ma MM , Xiaozhe Zhang PhD , Guifu Wu MD, PhD , Wendong Fan PhD
Hemodynamic shear stress is a frictional force that acts on vascular endothelial cells and is essential for endothelial homeostasis. Physiological laminar shear stress (LSS) suppresses endothelial inflammation and protects arteries from atherosclerosis. Herein, we screened differentially expressed circular RNAs (circRNAs) that were significantly altered in LSS-stimulated endothelial cells and found that circRNA-LONP2 was involved in modulating the flow-dependent inflammatory response. Furthermore, endothelial circRNA-LONP2 overexpression promoted endothelial inflammation and atherosclerosis in vitro and in vivo. Mechanistically, circRNA-LONP2 competitively sponged miR-200a-3p and subsequently promoted Kelch-like ECH-associated protein 1, Yes-associated protein 1, and enhancer of zeste homolog 2 expression, thereby inactivating nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling, promoting oxidative stress and endothelial inflammation, and accelerating atherosclerosis. LSS-induced down-regulation of circRNA-LONP2 suppresses endothelial inflammation, at least in part, by activating the miR-200a-3p–mediated nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling pathway. CircRNA-LONP2 may serve as a new therapeutic target for atherosclerosis.
{"title":"Shear-Sensitive circRNA-LONP2 Promotes Endothelial Inflammation and Atherosclerosis by Targeting NRF2/HO1 Signaling","authors":"Ruoyu Wang MM , Yue Zeng MM , Ziqi Chen PhD , Dongwei Ma MM , Xiaozhe Zhang PhD , Guifu Wu MD, PhD , Wendong Fan PhD","doi":"10.1016/j.jacbts.2024.02.019","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.02.019","url":null,"abstract":"<div><p>Hemodynamic shear stress is a frictional force that acts on vascular endothelial cells and is essential for endothelial homeostasis. Physiological laminar shear stress (LSS) suppresses endothelial inflammation and protects arteries from atherosclerosis. Herein, we screened differentially expressed circular RNAs (circRNAs) that were significantly altered in LSS-stimulated endothelial cells and found that circRNA-LONP2 was involved in modulating the flow-dependent inflammatory response. Furthermore, endothelial circRNA-LONP2 overexpression promoted endothelial inflammation and atherosclerosis in vitro and in vivo. Mechanistically, circRNA-LONP2 competitively sponged miR-200a-3p and subsequently promoted Kelch-like ECH-associated protein 1, Yes-associated protein 1, and enhancer of zeste homolog 2 expression, thereby inactivating nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling, promoting oxidative stress and endothelial inflammation, and accelerating atherosclerosis. LSS-induced down-regulation of circRNA-LONP2 suppresses endothelial inflammation, at least in part, by activating the miR-200a-3p–mediated nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling pathway. CircRNA-LONP2 may serve as a new therapeutic target for atherosclerosis.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001013/pdfft?md5=40566b453eaf52a13c53e7ce20a89fba&pid=1-s2.0-S2452302X24001013-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141241294","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 : 2024-05-01DOI: 10.1016/j.jacbts.2024.01.010
Sohel M. Julovi MBBS, PhD , Katie Trinh BSc(Adv), MBBS , Harry Robertson BMedSc(Hons-I) , Cuicui Xu BSc, PhD , Nikita Minhas PhD , Seethalakshmi Viswanathan MBBS , Ellis Patrick BSc(Hons), PhD , John D. Horowitz MBBS, PhD , Daniel N. Meijles PhD , Natasha M. Rogers MBBS(Hons), PhD
Patients with chronic kidney disease (CKD) face a high risk of cardiovascular disease. Previous studies reported that endogenous thrombospondin 1 (TSP1) involves right ventricular remodeling and dysfunction. Here we show that a murine model of CKD increased myocardial TSP1 expression and produced left ventricular hypertrophy, fibrosis, and dysfunction. TSP1 knockout mice were protected from these features. In vitro, indoxyl sulfate is driving deleterious changes in cardiomyocyte through the TSP1. In patients with CKD, TSP1 and aryl hydrocarbon receptor were both differentially expressed in the myocardium. Our findings summon large clinical studies to confirm the translational role of TSP1 in patients with CKD.
{"title":"Thrombospondin-1 Drives Cardiac Remodeling in Chronic Kidney Disease","authors":"Sohel M. Julovi MBBS, PhD , Katie Trinh BSc(Adv), MBBS , Harry Robertson BMedSc(Hons-I) , Cuicui Xu BSc, PhD , Nikita Minhas PhD , Seethalakshmi Viswanathan MBBS , Ellis Patrick BSc(Hons), PhD , John D. Horowitz MBBS, PhD , Daniel N. Meijles PhD , Natasha M. Rogers MBBS(Hons), PhD","doi":"10.1016/j.jacbts.2024.01.010","DOIUrl":"10.1016/j.jacbts.2024.01.010","url":null,"abstract":"<div><p>Patients with chronic kidney disease (CKD) face a high risk of cardiovascular disease. Previous studies reported that endogenous thrombospondin 1 (TSP1) involves right ventricular remodeling and dysfunction. Here we show that a murine model of CKD increased myocardial TSP1 expression and produced left ventricular hypertrophy, fibrosis, and dysfunction. TSP1 knockout mice were protected from these features. In vitro, indoxyl sulfate is driving deleterious changes in cardiomyocyte through the TSP1. In patients with CKD, TSP1 and aryl hydrocarbon receptor were both differentially expressed in the myocardium. Our findings summon large clinical studies to confirm the translational role of TSP1 in patients with CKD.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000378/pdfft?md5=1bebe1fb29e4a8ad99df4bc1befd59eb&pid=1-s2.0-S2452302X24000378-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140404688","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 : 2024-05-01DOI: 10.1016/j.jacbts.2024.04.002
Md Abul Hassan Samee PhD , James F. Martin MD, PhD
{"title":"Deep Image Segmentation for Cardiomyocyte Proliferation∗","authors":"Md Abul Hassan Samee PhD , James F. Martin MD, PhD","doi":"10.1016/j.jacbts.2024.04.002","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.04.002","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001402/pdfft?md5=2ef2af26a2365322bc925b5bb7887d50&pid=1-s2.0-S2452302X24001402-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141241293","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 : 2024-05-01DOI: 10.1016/j.jacbts.2024.01.017
Hao Cheng MD, PhD , Jian Wu MD, PhD , Linnan Li MD, PhD , Xiaoyue Song MD, PhD , Junqiang Xue MD, PhD , Yuekai Shi MD, PhD , Yunzeng Zou MD, PhD , Jianying Ma MD, PhD , Junbo Ge MD, PhD
RNA-binding proteins play multiple roles in several biological processes. However, the roles of RBM15—an important RNA-binding protein and a significant regulator of RNA methylation—in cardiovascular diseases remain elusive. This study aimed to investigate the biological function of RBM15 and its fundamental mechanisms in myocardial infarction (MI). Methylated RNA immunoprecipitation sequencing was used to explore the N6-methyladenosine (m6A) difference between MI and normal tissues. Our findings showed the elevated level of m6A in MI, and its transcription profile in both MI and normal tissues. RBM15 was the main regulator and its overexpression attenuated apoptosis in cardiomyocytes and improved cardiac function in mice after MI. Then, we used one target NEDD8 activating enzyme E1 subunit and its inhibitor (MLN4924) to investigate the impact of RBM15 targets on cardiomyocytes. Finally, the enhanced m6A methylation in the presence of RBM15 overexpression led to the increased expression and stability of NEDD8 activating enzyme E1 subunit. Our findings suggest that the enhanced m6A level is a protective mechanism in MI, and RBM15 is significantly upregulated in MI and promotes cardiac function. This study showed that RBM15 affected MI by stabilizing its target on the cell apoptosis function, which might provide a new insight into MI therapy.
{"title":"RBM15 Protects From Myocardial Infarction by Stabilizing NAE1","authors":"Hao Cheng MD, PhD , Jian Wu MD, PhD , Linnan Li MD, PhD , Xiaoyue Song MD, PhD , Junqiang Xue MD, PhD , Yuekai Shi MD, PhD , Yunzeng Zou MD, PhD , Jianying Ma MD, PhD , Junbo Ge MD, PhD","doi":"10.1016/j.jacbts.2024.01.017","DOIUrl":"10.1016/j.jacbts.2024.01.017","url":null,"abstract":"<div><p>RNA-binding proteins play multiple roles in several biological processes. However, the roles of RBM15—an important RNA-binding protein and a significant regulator of RNA methylation—in cardiovascular diseases remain elusive. This study aimed to investigate the biological function of RBM15 and its fundamental mechanisms in myocardial infarction (MI). Methylated RNA immunoprecipitation sequencing was used to explore the N6-methyladenosine (m<sup>6</sup>A) difference between MI and normal tissues. Our findings showed the elevated level of m<sup>6</sup>A in MI, and its transcription profile in both MI and normal tissues. RBM15 was the main regulator and its overexpression attenuated apoptosis in cardiomyocytes and improved cardiac function in mice after MI. Then, we used one target NEDD8 activating enzyme E1 subunit and its inhibitor (MLN4924) to investigate the impact of RBM15 targets on cardiomyocytes. Finally, the enhanced m<sup>6</sup>A methylation in the presence of RBM15 overexpression led to the increased expression and stability of NEDD8 activating enzyme E1 subunit. Our findings suggest that the enhanced m<sup>6</sup>A level is a protective mechanism in MI, and RBM15 is significantly upregulated in MI and promotes cardiac function. This study showed that RBM15 affected MI by stabilizing its target on the cell apoptosis function, which might provide a new insight into MI therapy.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000469/pdfft?md5=a927496e84ee2a7355f7b36d7c06a981&pid=1-s2.0-S2452302X24000469-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140756421","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}