Nature cardiovascular research最新文献_第10页

Semaphorin-3A regulates liver sinusoidal endothelial cell porosity and promotes hepatic steatosis 半aphorin-3A 调节肝窦内皮细胞孔隙率并促进肝脂肪变性

Nature cardiovascular research Pub Date : 2024-06-14 DOI: 10.1038/s44161-024-00487-z

Daniel Eberhard, Sydney Balkenhol, Andrea Köster, Paula Follert, Eric Upschulte, Philipp Ostermann, Philip Kirschner, Celina Uhlemeyer, Iannis Charnay, Christina Preuss, Sandra Trenkamp, Bengt-Frederik Belgardt, Timo Dickscheid, Irene Esposito, Michael Roden, Eckhard Lammert

{"title":"Semaphorin-3A regulates liver sinusoidal endothelial cell porosity and promotes hepatic steatosis","authors":"Daniel Eberhard, Sydney Balkenhol, Andrea Köster, Paula Follert, Eric Upschulte, Philipp Ostermann, Philip Kirschner, Celina Uhlemeyer, Iannis Charnay, Christina Preuss, Sandra Trenkamp, Bengt-Frederik Belgardt, Timo Dickscheid, Irene Esposito, Michael Roden, Eckhard Lammert","doi":"10.1038/s44161-024-00487-z","DOIUrl":"10.1038/s44161-024-00487-z","url":null,"abstract":"Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, increases worldwide and associates with type 2 diabetes and other cardiometabolic diseases. Here we demonstrate that Sema3a is elevated in liver sinusoidal endothelial cells of animal models for obesity, type 2 diabetes and MASLD. In primary human liver sinusoidal endothelial cells, saturated fatty acids induce expression of SEMA3A, and loss of a single allele is sufficient to reduce hepatic fat content in diet-induced obese mice. We show that semaphorin-3A regulates the number of fenestrae through a signaling cascade that involves neuropilin-1 and phosphorylation of cofilin-1 by LIM domain kinase 1. Finally, inducible vascular deletion of Sema3a in adult diet-induced obese mice reduces hepatic fat content and elevates very low-density lipoprotein secretion. Thus, we identified a molecular pathway linking hyperlipidemia to microvascular defenestration and early development of MASLD. Eberhard et al. show that SEMA3A regulates liver sinusoidal endothelial cell fenestrations by signaling through NRP1 and LIMK1, revealing a pathway that connects hyperlipidemia to the development of steatotic liver disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 6","pages":"734-753"},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00487-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141341749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of fenestrae in liver sinusoidal endothelial cells contributes to MASLD 肝窦内皮细胞栅栏的缺失是导致 MASLD 的原因之一

Nature cardiovascular research Pub Date : 2024-06-14 DOI: 10.1038/s44161-024-00490-4

Nadia Ciriaci, Pierre-Emmanuel Rautou, Johanne Poisson

引用次数: 0

Systemic and local regulation of hematopoietic homeostasis in health and disease 健康和疾病中造血平衡的系统和局部调节

Nature cardiovascular research Pub Date : 2024-06-12 DOI: 10.1038/s44161-024-00482-4

Randall S. Carpenter, Maria Maryanovich

{"title":"Systemic and local regulation of hematopoietic homeostasis in health and disease","authors":"Randall S. Carpenter, Maria Maryanovich","doi":"10.1038/s44161-024-00482-4","DOIUrl":"10.1038/s44161-024-00482-4","url":null,"abstract":"Hematopoietic stem cells (HSCs) generate all blood cell lineages responsible for tissue oxygenation, life-long hematopoietic homeostasis and immune protection. In adulthood, HSCs primarily reside in the bone marrow (BM) microenvironment, consisting of diverse cell types that constitute the stem cell ‘niche’. The adaptability of the hematopoietic system is required to respond to the needs of the host, whether to maintain normal physiology or during periods of physical, psychosocial or environmental stress. Hematopoietic homeostasis is achieved by intricate coordination of systemic and local factors that orchestrate the function of HSCs throughout life. However, homeostasis is not a static process; it modulates HSC and progenitor activity in response to circadian rhythms coordinated by the central and peripheral nervous systems, inflammatory cues, metabolites and pathologic conditions. Here, we review local and systemic factors that impact hematopoiesis, focusing on the implications of aging, stress and cardiovascular disease. Carpenter and Maryanovich explore how hematopoietic homeostasis, governed by local niche and systemic mechanisms, is impacted by environmental and immune stressors like stress, sleep patterns, aging and inflammation and examine the implications for cardiovascular diseases.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 6","pages":"651-665"},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141351724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Macrophages behave like mural cells to promote healing of ischemic muscle injury 巨噬细胞像壁细胞一样促进缺血性肌肉损伤的愈合

Nature cardiovascular research Pub Date : 2024-06-11 DOI: 10.1038/s44161-024-00479-z

引用次数: 0

Semaglutide improves cardiovascular health independently of weight loss 塞马鲁肽改善心血管健康与减轻体重无关

Nature cardiovascular research Pub Date : 2024-06-07 DOI: 10.1038/s44161-024-00499-9

Michelle Korda

引用次数: 0

Network-based prioritization and validation of regulators of vascular smooth muscle cell proliferation in disease 基于网络的疾病中血管平滑肌细胞增殖调节因子的优先排序和验证

Nature cardiovascular research Pub Date : 2024-06-06 DOI: 10.1038/s44161-024-00474-4

Jordi Lambert, Sebnem Oc, Matthew D. Worssam, Daniel Häußler, Charles U. Solomon, Nichola L. Figg, Ruby Baxter, Maria Imaz, James C. K. Taylor, Kirsty Foote, Alison Finigan, Krishnaa T. Mahbubani, Tom R. Webb, Shu Ye, Martin R. Bennett, Achim Krüger, Mikhail Spivakov, Helle F. Jørgensen

{"title":"Network-based prioritization and validation of regulators of vascular smooth muscle cell proliferation in disease","authors":"Jordi Lambert, Sebnem Oc, Matthew D. Worssam, Daniel Häußler, Charles U. Solomon, Nichola L. Figg, Ruby Baxter, Maria Imaz, James C. K. Taylor, Kirsty Foote, Alison Finigan, Krishnaa T. Mahbubani, Tom R. Webb, Shu Ye, Martin R. Bennett, Achim Krüger, Mikhail Spivakov, Helle F. Jørgensen","doi":"10.1038/s44161-024-00474-4","DOIUrl":"10.1038/s44161-024-00474-4","url":null,"abstract":"Aberrant vascular smooth muscle cell (VSMC) homeostasis and proliferation characterize vascular diseases causing heart attack and stroke. Here we elucidate molecular determinants governing VSMC proliferation by reconstructing gene regulatory networks from single-cell transcriptomics and epigenetic profiling. We detect widespread activation of enhancers at disease-relevant loci in proliferation-predisposed VSMCs. We compared gene regulatory network rewiring between injury-responsive and nonresponsive VSMCs, which suggested shared transcription factors but differing target loci between VSMC states. Through in silico perturbation analysis, we identified and prioritized previously unrecognized regulators of proliferation, including RUNX1 and TIMP1. Moreover, we showed that the pioneer transcription factor RUNX1 increased VSMC responsiveness and that TIMP1 feeds back to promote VSMC proliferation through CD74-mediated STAT3 signaling. Both RUNX1 and the TIMP1–CD74 axis were expressed in human VSMCs, showing low levels in normal arteries and increased expression in disease, suggesting clinical relevance and potential as vascular disease targets. Lambert, Oc et al. reconstruct gene regulatory networks from single-cell transcriptomics and epigenetic profiling, compare mouse and human data, and report previously unrecognized regulators of vascular smooth muscle cell proliferation in disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 6","pages":"714-733"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00474-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141377420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Age-dependent shortcut of the platelet differentiation cascade drives thrombocytosis and thrombotic diseases 血小板分化级联随年龄增长而缩短，导致血小板增多和血栓性疾病

Nature cardiovascular research Pub Date : 2024-06-06 DOI: 10.1038/s44161-024-00501-4

Gerburg Schwaerzer

引用次数: 0

Trimming down with semaglutide improves cardiac health in non-diabetic patients 使用塞马鲁肽减肥可改善非糖尿病患者的心脏健康

Nature cardiovascular research Pub Date : 2024-06-06 DOI: 10.1038/s44161-024-00498-w

Andrea Tavosanis

引用次数: 0

Macrophages upregulate mural cell-like markers and support healing of ischemic injury by adopting functions important for vascular support 巨噬细胞上调壁细胞样标志物，并通过承担对血管支持很重要的功能来支持缺血性损伤的愈合

Nature cardiovascular research Pub Date : 2024-06-06 DOI: 10.1038/s44161-024-00478-0

Catarina Amoedo-Leite, Kristel Parv, Chiara Testini, Carmen Herrera-Hidalgo, Feifei Xu, Antoine Giraud, Marta Malaquias, Erik Fasterius, Daniel Holl, Cedric Seignez, Christian Göritz, Gustaf Christoffersson, Mia Phillipson

{"title":"Macrophages upregulate mural cell-like markers and support healing of ischemic injury by adopting functions important for vascular support","authors":"Catarina Amoedo-Leite, Kristel Parv, Chiara Testini, Carmen Herrera-Hidalgo, Feifei Xu, Antoine Giraud, Marta Malaquias, Erik Fasterius, Daniel Holl, Cedric Seignez, Christian Göritz, Gustaf Christoffersson, Mia Phillipson","doi":"10.1038/s44161-024-00478-0","DOIUrl":"10.1038/s44161-024-00478-0","url":null,"abstract":"Sterile inflammation after injury is important for tissue restoration. In injured human and mouse tissues, macrophages were recently found to accumulate perivascularly. This study investigates if macrophages adopt a mural cell phenotype important for restoration after ischemic injury. Single-cell RNA sequencing of fate-mapped macrophages from ischemic mouse muscles demonstrates a macrophage-toward-mural cell switch of a subpopulation of macrophages with downregulated myeloid cell genes and upregulated mural cell genes, including PDGFRβ. This observation was further strengthened when including unspliced transcripts in the analysis. The macrophage switch was proven functionally relevant, as induction of macrophage-specific PDGFRβ deficiency prevented their perivascular macrophage phenotype, impaired vessel maturation and increased vessel leakiness, which ultimately reduced limb function. In conclusion, macrophages in adult ischemic tissue were demonstrated to undergo a cellular program to morphologically, transcriptomically and functionally resemble mural cells while weakening their macrophage identity. The macrophage-to-mural cell-like phenotypic switch is crucial for restoring tissue function and warrants further exploration as a potential target for immunotherapies to enhance healing. Amoedo-Leite et al. report that, in ischemic tissue, a subset of macrophages adopts mural cell-like morphology, gene expression and function, which is crucial for injury healing.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 6","pages":"685-700"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00478-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141378906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A self-reinforcing cycle hypothesis in heart failure pathogenesis 心力衰竭发病机制中的自我强化循环假说

Nature cardiovascular research Pub Date : 2024-06-03 DOI: 10.1038/s44161-024-00480-6

Carlos Fernandez-Patron, Gary D. Lopaschuk, Eugenio Hardy

{"title":"A self-reinforcing cycle hypothesis in heart failure pathogenesis","authors":"Carlos Fernandez-Patron, Gary D. Lopaschuk, Eugenio Hardy","doi":"10.1038/s44161-024-00480-6","DOIUrl":"10.1038/s44161-024-00480-6","url":null,"abstract":"Heart failure is a progressive syndrome with high morbidity and mortality rates. Here, we suggest that chronic exposure of the heart to risk factors for heart failure damages heart mitochondria, thereby impairing energy production to levels that can suppress the heart’s ability to pump blood and repair mitochondria (both energy-consuming processes). As damaged mitochondria accumulate, the heart becomes deprived of energy in a ‘self-reinforcing cycle’, which can persist after the heart is no longer chronically exposed to (or after antagonism of) the risk factors that initiated the cycle. Together with other previously described pathological mechanisms, this proposed cycle can help explain (1) why heart failure progresses, (2) why it can recur after cessation of treatment, and (3) why heart failure is often accompanied by dysfunction of multiple organs. Ideally, therapy of heart failure syndrome would be best attempted before the self-reinforcing cycle is triggered or designed to break the self-reinforcing cycle. Fernandez-Patron et al. propose a unifying framework explaining how diverse risk factors such as hypertension, obesity and diabetes lead pathogenesis and progression of heart failure.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 6","pages":"627-636"},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141272025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0