Pub Date : 2024-09-01DOI: 10.1016/j.jacbts.2024.05.013
Rose Pedretti BS , Lanie Wang BS , Anna Yakubovska MS , Qiongfang S. Zhang BS , Binh Nguyen PhD , Justin L. Grodin MD , Ahmad Masri MD , Lorena Saelices PhD
Amyloidogenic transthyretin (ATTR) amyloidosis is a relentlessly progressive disease caused by the misfolding and systemic accumulation of amyloidogenic transthyretin into amyloid fibrils. These fibrils cause diverse clinical phenotypes, mainly cardiomyopathy and/or polyneuropathy. Little is known about the aggregation of transthyretin during disease development and whether this has implications for diagnosis and treatment. Using the cryogenic electron microscopy structures of mature ATTR fibrils, we developed a peptide probe for fibril detection. With this probe, we have identified previously unknown aggregated transthyretin species in plasma of patients with ATTR amyloidosis. These species are large, non-native, and distinct from monomeric and tetrameric transthyretin. Observations from our study open many questions about the biology of ATTR amyloidosis and reveal a potential diagnostic and therapeutic target.
{"title":"Structure-Based Probe Reveals the Presence of Large Transthyretin Aggregates in Plasma of ATTR Amyloidosis Patients","authors":"Rose Pedretti BS , Lanie Wang BS , Anna Yakubovska MS , Qiongfang S. Zhang BS , Binh Nguyen PhD , Justin L. Grodin MD , Ahmad Masri MD , Lorena Saelices PhD","doi":"10.1016/j.jacbts.2024.05.013","DOIUrl":"10.1016/j.jacbts.2024.05.013","url":null,"abstract":"<div><div>Amyloidogenic transthyretin (ATTR) amyloidosis is a relentlessly progressive disease caused by the misfolding and systemic accumulation of amyloidogenic transthyretin into amyloid fibrils. These fibrils cause diverse clinical phenotypes, mainly cardiomyopathy and/or polyneuropathy. Little is known about the aggregation of transthyretin during disease development and whether this has implications for diagnosis and treatment. Using the cryogenic electron microscopy structures of mature ATTR fibrils, we developed a peptide probe for fibril detection. With this probe, we have identified previously unknown aggregated transthyretin species in plasma of patients with ATTR amyloidosis. These species are large, non-native, and distinct from monomeric and tetrameric transthyretin. Observations from our study open many questions about the biology of ATTR amyloidosis and reveal a potential diagnostic and therapeutic target.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1088-1100"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002201/pdfft?md5=5b6a105e3917c13332161203cd4e2112&pid=1-s2.0-S2452302X24002201-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248574","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 : 2024-09-01DOI: 10.1016/j.jacbts.2024.07.010
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.2024.07.010","DOIUrl":"10.1016/j.jacbts.2024.07.010","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Page 1162"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002900/pdfft?md5=1141885f18877b300920fcb40d32afd6&pid=1-s2.0-S2452302X24002900-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310569","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 : 2024-09-01DOI: 10.1016/j.jacbts.2024.05.006
Yuxin Bu MM , Yanxia Liu MD , Meili Liu MD, Chenghui Yan MD, Jing Wang MM, Hanlin Wu MM, Haixu Song MD, Dali Zhang MD, Kai Xu MD, Dan Liu MD, Yaling Han MD, PhD
Tripartite motif-containing 55 (Trim55) is mainly expressed in myocardium and skeletal muscle, which plays an important role in promoting the embryonic development of the mouse heart. We investigated the role of Trim55 in myocardial infarction and the associated molecular mechanisms. We studied both gain and loss of function in vivo and in vitro. The results showed that Trim55 knockout improved cardiac function and apoptosis after myocardial infarction, and overexpression aggravated cardiac function damage. The mechanism is that Trim55 interacts with nuclear factor, erythroid derived 2 (Nrf2) to accelerate its degradation and inhibit the expression of heme oxygenase 1, thereby promoting cardiomyocyte apoptosis.
{"title":"TRIM55 Aggravates Cardiomyocyte Apoptosis After Myocardial Infarction via Modulation of the Nrf2/HO-1 Pathway","authors":"Yuxin Bu MM , Yanxia Liu MD , Meili Liu MD, Chenghui Yan MD, Jing Wang MM, Hanlin Wu MM, Haixu Song MD, Dali Zhang MD, Kai Xu MD, Dan Liu MD, Yaling Han MD, PhD","doi":"10.1016/j.jacbts.2024.05.006","DOIUrl":"10.1016/j.jacbts.2024.05.006","url":null,"abstract":"<div><div>Tripartite motif-containing 55 (Trim55) is mainly expressed in myocardium and skeletal muscle, which plays an important role in promoting the embryonic development of the mouse heart. We investigated the role of Trim55 in myocardial infarction and the associated molecular mechanisms. We studied both gain and loss of function in vivo and in vitro. The results showed that Trim55 knockout improved cardiac function and apoptosis after myocardial infarction, and overexpression aggravated cardiac function damage. The mechanism is that Trim55 interacts with nuclear factor, erythroid derived 2 (Nrf2) to accelerate its degradation and inhibit the expression of heme oxygenase 1, thereby promoting cardiomyocyte apoptosis.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1104-1122"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002134/pdfft?md5=017379718d1c2bd24f63c67d39e1d9dd&pid=1-s2.0-S2452302X24002134-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248573","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 : 2024-09-01DOI: 10.1016/j.jacbts.2024.05.014
Marcin A. Sowa PhD , Haoyu Sun PhD , Tricia T. Wang BA , Vitor W. Virginio PhD , Florencia Schlamp PhD , Hanane El Bannoudi PhD , MacIntosh Cornwell PhD , Hannah Bash BA , Peter M. Izmirly MD , H. Michael Belmont MD , Kelly V. Ruggles PhD , Jill P. Buyon MD , Deepak Voora MD , Tessa J. Barrett PhD , Jeffrey S. Berger MD
The authors investigated the impact of antiplatelet therapy on the megakaryocyte (MK) and platelet transcriptome. RNA-sequencing was performed on MKs treated with aspirin or P2Y12 inhibitor, platelets from healthy volunteers receiving aspirin or P2Y12 inhibition, and platelets from patients with systemic lupus erythematosus (SLE). P2Y12 inhibition reduced gene expression and inflammatory pathways in MKs and platelets. In SLE, the interferon (IFN) pathway was elevated. In vitro experiments demonstrated the role of P2Y12 inhibition in reducing IFNα-induced platelet-leukocyte interactions and IFN signaling pathways. These results suggest that P2Y12 inhibition may have therapeutic potential for proinflammatory and autoimmune conditions like SLE.
{"title":"Inhibiting the P2Y12 Receptor in Megakaryocytes and Platelets Suppresses Interferon-Associated Responses","authors":"Marcin A. Sowa PhD , Haoyu Sun PhD , Tricia T. Wang BA , Vitor W. Virginio PhD , Florencia Schlamp PhD , Hanane El Bannoudi PhD , MacIntosh Cornwell PhD , Hannah Bash BA , Peter M. Izmirly MD , H. Michael Belmont MD , Kelly V. Ruggles PhD , Jill P. Buyon MD , Deepak Voora MD , Tessa J. Barrett PhD , Jeffrey S. Berger MD","doi":"10.1016/j.jacbts.2024.05.014","DOIUrl":"10.1016/j.jacbts.2024.05.014","url":null,"abstract":"<div><div>The authors investigated the impact of antiplatelet therapy on the megakaryocyte (MK) and platelet transcriptome. RNA-sequencing was performed on MKs treated with aspirin or P2Y<sub>12</sub> inhibitor, platelets from healthy volunteers receiving aspirin or P2Y<sub>12</sub> inhibition, and platelets from patients with systemic lupus erythematosus (SLE). P2Y<sub>12</sub> inhibition reduced gene expression and inflammatory pathways in MKs and platelets. In SLE, the interferon (IFN) pathway was elevated. In vitro experiments demonstrated the role of P2Y<sub>12</sub> inhibition in reducing IFNα-induced platelet-leukocyte interactions and IFN signaling pathways. These results suggest that P2Y<sub>12</sub> inhibition may have therapeutic potential for proinflammatory and autoimmune conditions like SLE.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1126-1140"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002213/pdfft?md5=7f2c6a99acc7a7dc4600a00905868755&pid=1-s2.0-S2452302X24002213-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141840267","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 : 2024-09-01DOI: 10.1016/j.jacbts.2024.05.016
Pedro Giro MD , Mallory Filipp PhD , Michael J. Zhang MD, PhD , Ethan D. Moser MPH , Edward B. Thorp PhD , Prarthana J. Dalal MD, PhD , Ravi V. Shah MD , Patrick T. Ellinor MD, PhD , Jonathan W. Cunningham MD , Sean J. Jurgens MD, MSc , Arjun Sinha MD, MSc , Laura Rasmussen-Torvik PhD, MPH , Jorge Kizer MD, MSc , Kent D. Taylor PhD , Philip Greenland MD , Bruce M. Psaty MD, PhD , Russell P. Tracy PhD , Lin Yee Chen MD, MS , Amil M. Shah MD , Bing Yu PhD , Ravi B. Patel MD, MSc
A common missense variant in ICAM1 among African American individuals (rs5491; pK56M) has been associated with risk of heart failure with preserved ejection fraction (HFpEF), but the pathways that lead to HFpEF among those with this variant are not clear. In this analysis of 92 circulating proteins and their associated networks, we identified 7 circulating inflammatory proteins associated with rs5491 among >600 African American individuals. Using weighted coexpression network analysis, 3 protein networks were identified, one of which was associated with rs5491. This protein network was most highly represented by members of the tumor necrosis receptor superfamily. The rs5491 variant demonstrated an inflammatory proteomic profile in a separate cohort of African American individuals. This analysis identifies inflammatory pathways that may drive HFpEF among African American individuals with the ICAM1 pK56M (rs5491) variant.
{"title":"Proteomic Profile of the ICAM1 p.K56M HFpEF Risk Variant","authors":"Pedro Giro MD , Mallory Filipp PhD , Michael J. Zhang MD, PhD , Ethan D. Moser MPH , Edward B. Thorp PhD , Prarthana J. Dalal MD, PhD , Ravi V. Shah MD , Patrick T. Ellinor MD, PhD , Jonathan W. Cunningham MD , Sean J. Jurgens MD, MSc , Arjun Sinha MD, MSc , Laura Rasmussen-Torvik PhD, MPH , Jorge Kizer MD, MSc , Kent D. Taylor PhD , Philip Greenland MD , Bruce M. Psaty MD, PhD , Russell P. Tracy PhD , Lin Yee Chen MD, MS , Amil M. Shah MD , Bing Yu PhD , Ravi B. Patel MD, MSc","doi":"10.1016/j.jacbts.2024.05.016","DOIUrl":"10.1016/j.jacbts.2024.05.016","url":null,"abstract":"<div><div>A common missense variant in <em>ICAM1</em> among African American individuals (rs5491; pK56M) has been associated with risk of heart failure with preserved ejection fraction (HFpEF), but the pathways that lead to HFpEF among those with this variant are not clear. In this analysis of 92 circulating proteins and their associated networks, we identified 7 circulating inflammatory proteins associated with rs5491 among >600 African American individuals. Using weighted coexpression network analysis, 3 protein networks were identified, one of which was associated with rs5491. This protein network was most highly represented by members of the tumor necrosis receptor superfamily. The rs5491 variant demonstrated an inflammatory proteomic profile in a separate cohort of African American individuals. This analysis identifies inflammatory pathways that may drive HFpEF among African American individuals with the <em>ICAM1</em> pK56M (rs5491) variant.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1073-1084"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002262/pdfft?md5=6a8e1da15f7d8bf280efb89154fd82d8&pid=1-s2.0-S2452302X24002262-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248572","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}
Coronary artery disease (CAD) is a major health issue. This study focused on pericardial macrophages and small extracellular vesicles (sEVs) in CAD. The macrophages in CAD patients showed reduced expression of protective markers and unchanged levels of proinflammatory receptors. Similar changes were observed in buffy-coat–derived macrophages when stimulated with CAD pericardial fluid-derived sEVs. The sEV contained miRNA-6516-5p, which inhibited CD36 and affected macrophage lipid uptake. These findings indicate that sEV-mediated miRNA actions contribute to the decrease in protective pericardial macrophages in CAD.
{"title":"Small Extracellular Vesicles in the Pericardium Modulate Macrophage Immunophenotype in Coronary Artery Disease","authors":"Soumaya Ben-Aicha PhD , Maryam Anwar PhD , Gemma Vilahur PhD , Fabiana Martino PhD , Panagiotis G. Kyriazis MSc , Natasha de Winter MSc , Prakash P. Punjabi MD, PhD , Gianni D. Angelini MD , Susanne Sattler PhD , Costanza Emanueli PhD","doi":"10.1016/j.jacbts.2024.05.003","DOIUrl":"10.1016/j.jacbts.2024.05.003","url":null,"abstract":"<div><div>Coronary artery disease (CAD) is a major health issue. This study focused on pericardial macrophages and small extracellular vesicles (sEVs) in CAD. The macrophages in CAD patients showed reduced expression of protective markers and unchanged levels of proinflammatory receptors. Similar changes were observed in buffy-coat–derived macrophages when stimulated with CAD pericardial fluid-derived sEVs. The sEV contained miRNA-6516-5p, which inhibited CD36 and affected macrophage lipid uptake. These findings indicate that sEV-mediated miRNA actions contribute to the decrease in protective pericardial macrophages in CAD.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1057-1072"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001888/pdfft?md5=a5069912a4a92134ebda4433d621f0d5&pid=1-s2.0-S2452302X24001888-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141703465","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 : 2024-09-01DOI: 10.1016/j.jacbts.2024.08.002
Douglas L. Mann MD (Editor-in-Chief, JACC: Basic to Translational Science)
{"title":"The Use of Digital Healthcare Twins in Early-Phase Clinical Trials","authors":"Douglas L. Mann MD (Editor-in-Chief, JACC: Basic to Translational Science)","doi":"10.1016/j.jacbts.2024.08.002","DOIUrl":"10.1016/j.jacbts.2024.08.002","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1159-1161"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002936/pdfft?md5=cb67a842585465ea6128136fadae1e91&pid=1-s2.0-S2452302X24002936-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310567","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号