Pub Date : 2024-11-18DOI: 10.1038/s41569-024-01100-3
Yvonne Baumer, Jason Irei, William A Boisvert
The presence of cholesterol crystals (CCs) in tissues was first described more than 100 years ago. CCs have a pathogenic role in various cardiovascular diseases, including myocardial infarction, aortic aneurysm and, most prominently, atherosclerosis. Although the underlying mechanisms and signalling pathways involved in CC formation are incompletely understood, numerous studies have highlighted the existence of CCs at various stages of atheroma progression. In this Review, we summarize the mechanisms underlying CC formation and the role of CCs in cardiovascular disease. In particular, we explore the established links between lipid metabolism across various cell types and the formation of CCs, with a focus on CC occurrence in the vasculature. We also discuss CC-induced inflammation as one of the pathogenic features of CCs in the atheroma. Finally, we summarize the therapeutic strategies aimed at reducing CC-mediated atherosclerotic burden, including approaches to inhibit CC formation in the vasculature or to mitigate the inflammatory response triggered by CCs. Addressing CC formation might emerge as a crucial component in our broader efforts to combat cardiovascular disease.
100 多年前，人们首次发现组织中存在胆固醇结晶（CCs）。CC 在多种心血管疾病中具有致病作用，包括心肌梗塞、主动脉瘤和最突出的动脉粥样硬化。尽管人们对 CC 形成的基本机制和信号通路尚不完全清楚，但许多研究都强调了 CC 在动脉粥样硬化进展的不同阶段的存在。在本综述中，我们总结了CC形成的基本机制以及CC在心血管疾病中的作用。特别是，我们探讨了各种细胞类型的脂质代谢与 CC 的形成之间的既定联系，重点是血管中 CC 的发生。我们还讨论了 CC 引发的炎症是动脉粥样斑块中 CC 的致病特征之一。最后，我们总结了旨在减轻CC介导的动脉粥样硬化负担的治疗策略，包括抑制血管中CC的形成或减轻CC引发的炎症反应的方法。在我们防治心血管疾病的更广泛努力中，解决 CC 形成问题可能会成为一个关键组成部分。
{"title":"Cholesterol crystals in the pathogenesis of atherosclerosis.","authors":"Yvonne Baumer, Jason Irei, William A Boisvert","doi":"10.1038/s41569-024-01100-3","DOIUrl":"https://doi.org/10.1038/s41569-024-01100-3","url":null,"abstract":"<p><p>The presence of cholesterol crystals (CCs) in tissues was first described more than 100 years ago. CCs have a pathogenic role in various cardiovascular diseases, including myocardial infarction, aortic aneurysm and, most prominently, atherosclerosis. Although the underlying mechanisms and signalling pathways involved in CC formation are incompletely understood, numerous studies have highlighted the existence of CCs at various stages of atheroma progression. In this Review, we summarize the mechanisms underlying CC formation and the role of CCs in cardiovascular disease. In particular, we explore the established links between lipid metabolism across various cell types and the formation of CCs, with a focus on CC occurrence in the vasculature. We also discuss CC-induced inflammation as one of the pathogenic features of CCs in the atheroma. Finally, we summarize the therapeutic strategies aimed at reducing CC-mediated atherosclerotic burden, including approaches to inhibit CC formation in the vasculature or to mitigate the inflammatory response triggered by CCs. Addressing CC formation might emerge as a crucial component in our broader efforts to combat cardiovascular disease.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668251","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}
Pub Date : 2024-11-15DOI: 10.1038/s41569-024-01098-8
Jianyi Jay Zhang, Steven M Pogwizd, Keiichi Fukuda, Wolfram-Hubertus Zimmermann, Chengming Fan, Joshua M Hare, Roberto Bolli, Philippe Menasché
Heart failure (HF) remains a leading cause of mortality, responsible for 13% of all deaths worldwide. The prognosis for patients with HF is poor, with only a 50% survival rate within 5 years. A major challenge of ischaemia-driven HF is the loss of cardiomyocytes, compounded by the minimal regenerative capacity of the adult heart. To date, replacement of irreversibly damaged heart muscle can only be achieved by complete heart transplantation. In the past 20 years, cell therapy has emerged and evolved as a promising avenue for cardiac repair and regeneration. During this time, cell therapy for HF has encountered substantial barriers in both preclinical studies and clinical trials but the field continues to progress and evolve from lessons learned from such research. In this Review, we provide an overview of ongoing trials of cell-based and cell product-based therapies for the treatment of HF. Findings from these trials will facilitate the clinical translation of cardiac regenerative and reparative therapies not only by evaluating the safety and efficacy of specific cell-based therapeutics but also by establishing the feasibility of novel or underexplored treatment protocols such as repeated intravenous dosing, personalized patient selection based on pharmacogenomics, systemic versus intramural cell delivery, and epicardial engraftment of engineered tissue products.
{"title":"Trials and tribulations of cell therapy for heart failure: an update on ongoing trials.","authors":"Jianyi Jay Zhang, Steven M Pogwizd, Keiichi Fukuda, Wolfram-Hubertus Zimmermann, Chengming Fan, Joshua M Hare, Roberto Bolli, Philippe Menasché","doi":"10.1038/s41569-024-01098-8","DOIUrl":"https://doi.org/10.1038/s41569-024-01098-8","url":null,"abstract":"<p><p>Heart failure (HF) remains a leading cause of mortality, responsible for 13% of all deaths worldwide. The prognosis for patients with HF is poor, with only a 50% survival rate within 5 years. A major challenge of ischaemia-driven HF is the loss of cardiomyocytes, compounded by the minimal regenerative capacity of the adult heart. To date, replacement of irreversibly damaged heart muscle can only be achieved by complete heart transplantation. In the past 20 years, cell therapy has emerged and evolved as a promising avenue for cardiac repair and regeneration. During this time, cell therapy for HF has encountered substantial barriers in both preclinical studies and clinical trials but the field continues to progress and evolve from lessons learned from such research. In this Review, we provide an overview of ongoing trials of cell-based and cell product-based therapies for the treatment of HF. Findings from these trials will facilitate the clinical translation of cardiac regenerative and reparative therapies not only by evaluating the safety and efficacy of specific cell-based therapeutics but also by establishing the feasibility of novel or underexplored treatment protocols such as repeated intravenous dosing, personalized patient selection based on pharmacogenomics, systemic versus intramural cell delivery, and epicardial engraftment of engineered tissue products.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639368","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}
Pub Date : 2024-11-14DOI: 10.1038/s41569-024-01099-7
Robert A Byrne, Adnan Kastrati
{"title":"Trade-offs between vessel-based and substrate-based nomenclatures for coronary heart diseases.","authors":"Robert A Byrne, Adnan Kastrati","doi":"10.1038/s41569-024-01099-7","DOIUrl":"10.1038/s41569-024-01099-7","url":null,"abstract":"","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624329","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}
Pub Date : 2024-11-14DOI: 10.1038/s41569-024-01102-1
Dong Zhao, Maria Rubini
{"title":"Improving English proficiency for scientific communication by non-fluent speakers.","authors":"Dong Zhao, Maria Rubini","doi":"10.1038/s41569-024-01102-1","DOIUrl":"10.1038/s41569-024-01102-1","url":null,"abstract":"","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624279","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}
Pub Date : 2024-11-14DOI: 10.1038/s41569-024-01106-x
Irene Fernández-Ruiz
{"title":"Monocytes migrate to the brain after MI to promote deep sleep to aid cardiac healing.","authors":"Irene Fernández-Ruiz","doi":"10.1038/s41569-024-01106-x","DOIUrl":"10.1038/s41569-024-01106-x","url":null,"abstract":"","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624324","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}
Pub Date : 2023-11-14DOI: 10.1038/s41569-023-00961-4
Gregory B. Lim
Activation of a specific set of vagal sensory neurons connecting the ventricular wall of the heart to the area postrema in the brainstem causes mice to faint. This finding defines a cardiac reflex that recapitulates characteristics of human syncope.
{"title":"Explaining how a cardiac reflex causes syncope","authors":"Gregory B. Lim","doi":"10.1038/s41569-023-00961-4","DOIUrl":"10.1038/s41569-023-00961-4","url":null,"abstract":"Activation of a specific set of vagal sensory neurons connecting the ventricular wall of the heart to the area postrema in the brainstem causes mice to faint. This finding defines a cardiac reflex that recapitulates characteristics of human syncope.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 1","pages":"9-9"},"PeriodicalIF":49.6,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591807","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}
Pub Date : 2023-11-14DOI: 10.1038/s41569-023-00960-5
Gregory B. Lim
Two new studies using cryo-electron microscopy describe the structure and conformation of myosin in the cardiac thick filaments and how it interacts with other thick-filament proteins, such as titin and cardiac myosin-binding protein C, in mammalian hearts.
{"title":"Revealing the structure of the cardiac myosin filament","authors":"Gregory B. Lim","doi":"10.1038/s41569-023-00960-5","DOIUrl":"10.1038/s41569-023-00960-5","url":null,"abstract":"Two new studies using cryo-electron microscopy describe the structure and conformation of myosin in the cardiac thick filaments and how it interacts with other thick-filament proteins, such as titin and cardiac myosin-binding protein C, in mammalian hearts.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 1","pages":"7-7"},"PeriodicalIF":49.6,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591808","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}
Pub Date : 2023-11-13DOI: 10.1038/s41569-023-00959-y
Irene Fernández-Ruiz
An approach that increases the expression of the chemokine receptor CXCR4 in vascular cells by targeting a microRNA-based repressive pathway attenuates atherosclerosis in mice and promotes atheroprotective functions in human and mouse vascular cells in vitro.
{"title":"Disrupting a cell-specific miRNA–CXCR4 interaction is atheroprotective in mice","authors":"Irene Fernández-Ruiz","doi":"10.1038/s41569-023-00959-y","DOIUrl":"10.1038/s41569-023-00959-y","url":null,"abstract":"An approach that increases the expression of the chemokine receptor CXCR4 in vascular cells by targeting a microRNA-based repressive pathway attenuates atherosclerosis in mice and promotes atheroprotective functions in human and mouse vascular cells in vitro.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 1","pages":"9-9"},"PeriodicalIF":49.6,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92155371","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}
Pub Date : 2023-11-08DOI: 10.1038/s41569-023-00947-2
Harpreet S. Bhatia, Richard C. Becker, Gregor Leibundgut, Mitul Patel, Paul Lacaze, Andrew Tonkin, Jagat Narula, Sotirios Tsimikas
Lipoprotein(a) (Lp(a)) is associated with atherothrombosis through several mechanisms, including putative antifibrinolytic properties. However, genetic association studies have not demonstrated an association between high plasma levels of Lp(a) and the risk of venous thromboembolism, and studies in patients with highly elevated Lp(a) levels have shown that Lp(a) lowering does not modify the clotting properties of plasma ex vivo. Lp(a) can interact with several platelet receptors, providing biological plausibility for a pro-aggregatory effect. Observational clinical studies suggest that elevated plasma Lp(a) concentrations are associated with worse long-term outcomes in patients undergoing revascularization. Furthermore, in these patients, those with elevated plasma Lp(a) levels derive more benefit from prolonged dual antiplatelet therapy than those with normal Lp(a) levels. The ASPREE trial in healthy older individuals treated with aspirin showed a reduction in ischaemic events in those who had a single-nucleotide polymorphism in LPA that is associated with elevated Lp(a) levels in plasma, without an increase in bleeding events. In this Review, we re-examine the role of Lp(a) in the regulation of platelet function and suggest areas of research to define further the clinical relevance to cardiovascular disease of the observed associations between Lp(a) and platelet function. In this Review, Tsimikas and co-workers re-examine the role of lipoprotein(a) in the regulation of platelet function and propose areas for future research to define its clinical relevance for cardiovascular disease.
{"title":"Lipoprotein(a), platelet function and cardiovascular disease","authors":"Harpreet S. Bhatia, Richard C. Becker, Gregor Leibundgut, Mitul Patel, Paul Lacaze, Andrew Tonkin, Jagat Narula, Sotirios Tsimikas","doi":"10.1038/s41569-023-00947-2","DOIUrl":"10.1038/s41569-023-00947-2","url":null,"abstract":"Lipoprotein(a) (Lp(a)) is associated with atherothrombosis through several mechanisms, including putative antifibrinolytic properties. However, genetic association studies have not demonstrated an association between high plasma levels of Lp(a) and the risk of venous thromboembolism, and studies in patients with highly elevated Lp(a) levels have shown that Lp(a) lowering does not modify the clotting properties of plasma ex vivo. Lp(a) can interact with several platelet receptors, providing biological plausibility for a pro-aggregatory effect. Observational clinical studies suggest that elevated plasma Lp(a) concentrations are associated with worse long-term outcomes in patients undergoing revascularization. Furthermore, in these patients, those with elevated plasma Lp(a) levels derive more benefit from prolonged dual antiplatelet therapy than those with normal Lp(a) levels. The ASPREE trial in healthy older individuals treated with aspirin showed a reduction in ischaemic events in those who had a single-nucleotide polymorphism in LPA that is associated with elevated Lp(a) levels in plasma, without an increase in bleeding events. In this Review, we re-examine the role of Lp(a) in the regulation of platelet function and suggest areas of research to define further the clinical relevance to cardiovascular disease of the observed associations between Lp(a) and platelet function. In this Review, Tsimikas and co-workers re-examine the role of lipoprotein(a) in the regulation of platelet function and propose areas for future research to define its clinical relevance for cardiovascular disease.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 5","pages":"299-311"},"PeriodicalIF":49.6,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483899","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}
Pub Date : 2023-11-06DOI: 10.1038/s41569-023-00956-1
Karina Huynh
In the LIFE-BTK trial, treatment with an everolimus-eluting resorbable scaffold was superior to angioplasty in improving clinical outcomes in patients with chronic limb-threatening ischaemia due to infrapopliteal artery disease.
{"title":"Drug-eluting resorbable scaffolds are superior to angioplasty for infrapopliteal artery disease","authors":"Karina Huynh","doi":"10.1038/s41569-023-00956-1","DOIUrl":"10.1038/s41569-023-00956-1","url":null,"abstract":"In the LIFE-BTK trial, treatment with an everolimus-eluting resorbable scaffold was superior to angioplasty in improving clinical outcomes in patients with chronic limb-threatening ischaemia due to infrapopliteal artery disease.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 1","pages":"8-8"},"PeriodicalIF":49.6,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483898","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}
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