Pub Date : 2024-06-27DOI: 10.1038/s44161-024-00504-1
Salim Abdelilah-Seyfried, Hanjoong Jo
The discovery of the genes causing cerebral cavernous malformation (CCM) initially heralded a fruitful search for etiopathogenic molecular pathways in this rare cerebrovascular disease. Recent studies have identified the relevance of CCM proteins for much more common vascular biology and pathologies.
{"title":"A renaissance of cerebral cavernous malformation proteins in vascular physiology","authors":"Salim Abdelilah-Seyfried, Hanjoong Jo","doi":"10.1038/s44161-024-00504-1","DOIUrl":"10.1038/s44161-024-00504-1","url":null,"abstract":"The discovery of the genes causing cerebral cavernous malformation (CCM) initially heralded a fruitful search for etiopathogenic molecular pathways in this rare cerebrovascular disease. Recent studies have identified the relevance of CCM proteins for much more common vascular biology and pathologies.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639679","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}
Pub Date : 2024-06-26DOI: 10.1038/s44161-024-00494-0
We describe the regenerative senescence signature of the injured mouse heart using proteomics and single-cell RNA sequencing. We report that transient senescence is required for neonatal mouse heart regeneration and for agrin-mediated cardiac repair in adult mice and provide insights into the essential role of Egr1 in senescence and regeneration.
{"title":"Cellular senescence is required for cardiac regeneration","authors":"","doi":"10.1038/s44161-024-00494-0","DOIUrl":"10.1038/s44161-024-00494-0","url":null,"abstract":"We describe the regenerative senescence signature of the injured mouse heart using proteomics and single-cell RNA sequencing. We report that transient senescence is required for neonatal mouse heart regeneration and for agrin-mediated cardiac repair in adult mice and provide insights into the essential role of Egr1 in senescence and regeneration.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980515","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}
Pub Date : 2024-06-18DOI: 10.1038/s44161-024-00489-x
Kensuke Sakata, Ryan P. Bradley, Adityo Prakosa, Carolyna A. P. Yamamoto, Syed Yusuf Ali, Shane Loeffler, Brock M. Tice, Patrick M. Boyle, Eugene G. Kholmovski, Ritu Yadav, Sunil Kumar Sinha, Joseph E. Marine, Hugh Calkins, David D. Spragg, Natalia A. Trayanova
Atrial fibrillation (AF), the most common heart rhythm disorder, may cause stroke and heart failure. For patients with persistent AF with fibrosis proliferation, the standard AF treatment—pulmonary vein isolation—has poor outcomes, necessitating redo procedures, owing to insufficient understanding of what constitutes good targets in fibrotic substrates. Here we present a prospective clinical and personalized digital twin study that characterizes the arrhythmogenic properties of persistent AF substrates and uncovers locations possessing rotor-attracting capabilities. Among these, a portion needs to be ablated to render the substrate not inducible for rotors, but the rest (37%) lose rotor-attracting capabilities when another location is ablated. Leveraging digital twin mechanistic insights, we suggest ablation targets that eliminate arrhythmia propensity with minimum lesions while also minimizing the risk of iatrogenic tachycardia and AF recurrence. Our findings provide further evidence regarding the appropriate substrate ablation targets in persistent AF, opening the door for effective strategies to mitigate patients’ AF burden. Sakata et al. performed a prospective personalized mechanistic computational (digital twin) study focused on characterizing the arrhythmogenic properties of the atrial fibrotic substrate in patients with persistent atrial fibrillation, and they introduce here a novel mechanism-oriented strategy for optimal ablation.
{"title":"Assessing the arrhythmogenic propensity of fibrotic substrate using digital twins to inform a mechanisms-based atrial fibrillation ablation strategy","authors":"Kensuke Sakata, Ryan P. Bradley, Adityo Prakosa, Carolyna A. P. Yamamoto, Syed Yusuf Ali, Shane Loeffler, Brock M. Tice, Patrick M. Boyle, Eugene G. Kholmovski, Ritu Yadav, Sunil Kumar Sinha, Joseph E. Marine, Hugh Calkins, David D. Spragg, Natalia A. Trayanova","doi":"10.1038/s44161-024-00489-x","DOIUrl":"10.1038/s44161-024-00489-x","url":null,"abstract":"Atrial fibrillation (AF), the most common heart rhythm disorder, may cause stroke and heart failure. For patients with persistent AF with fibrosis proliferation, the standard AF treatment—pulmonary vein isolation—has poor outcomes, necessitating redo procedures, owing to insufficient understanding of what constitutes good targets in fibrotic substrates. Here we present a prospective clinical and personalized digital twin study that characterizes the arrhythmogenic properties of persistent AF substrates and uncovers locations possessing rotor-attracting capabilities. Among these, a portion needs to be ablated to render the substrate not inducible for rotors, but the rest (37%) lose rotor-attracting capabilities when another location is ablated. Leveraging digital twin mechanistic insights, we suggest ablation targets that eliminate arrhythmia propensity with minimum lesions while also minimizing the risk of iatrogenic tachycardia and AF recurrence. Our findings provide further evidence regarding the appropriate substrate ablation targets in persistent AF, opening the door for effective strategies to mitigate patients’ AF burden. Sakata et al. performed a prospective personalized mechanistic computational (digital twin) study focused on characterizing the arrhythmogenic properties of the atrial fibrotic substrate in patients with persistent atrial fibrillation, and they introduce here a novel mechanism-oriented strategy for optimal ablation.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00489-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639676","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}
Pub Date : 2024-06-17DOI: 10.1038/s44161-024-00488-y
Jacob Bergstedt, Joëlle A. Pasman, Ziyan Ma, Arvid Harder, Shuyang Yao, Nadine Parker, Jorien L. Treur, Dirk J. A. Smit, Oleksandr Frei, Alexey A. Shadrin, Joeri J. Meijsen, Qing Shen, Sara Hägg, Per Tornvall, Alfonso Buil, Thomas Werge, Jens Hjerling-Leffler, Thomas D. Als, Anders D. Børglum, Cathryn M. Lewis, Andrew M. McIntosh, Unnur A. Valdimarsdóttir, Ole A. Andreassen, Patrick F. Sullivan, Yi Lu, Fang Fang
Major depressive disorder (MDD) and cardiovascular disease (CVD) are often comorbid, resulting in excess morbidity and mortality. Here we show that CVDs share most of their genetic risk factors with MDD. Multivariate genome-wide association analysis of shared genetic liability between MDD and atherosclerotic CVD revealed seven loci and distinct patterns of tissue and brain cell-type enrichments, suggesting the involvement of the thalamus. Part of the genetic overlap was explained by shared inflammatory, metabolic and psychosocial or lifestyle risk factors. Our data indicated causal effects of genetic liability to MDD on CVD risk, but not from most CVDs to MDD, and showed that the causal effects were partly explained by metabolic and psychosocial or lifestyle factors. The distinct signature of MDD–atherosclerotic CVD comorbidity suggests an immunometabolic subtype of MDD that is more strongly associated with CVD than overall MDD. In summary, we identified biological mechanisms underlying MDD–CVD comorbidity and modifiable risk factors for prevention of CVD in individuals with MDD. Bergstedt et al. show that the effects of genetic liability to major depressive disorder can cause an increase in cardiovascular risk and that metabolic, psychological and lifestyle factors are partly responsible for this association.
{"title":"Distinct biological signature and modifiable risk factors underlie the comorbidity between major depressive disorder and cardiovascular disease","authors":"Jacob Bergstedt, Joëlle A. Pasman, Ziyan Ma, Arvid Harder, Shuyang Yao, Nadine Parker, Jorien L. Treur, Dirk J. A. Smit, Oleksandr Frei, Alexey A. Shadrin, Joeri J. Meijsen, Qing Shen, Sara Hägg, Per Tornvall, Alfonso Buil, Thomas Werge, Jens Hjerling-Leffler, Thomas D. Als, Anders D. Børglum, Cathryn M. Lewis, Andrew M. McIntosh, Unnur A. Valdimarsdóttir, Ole A. Andreassen, Patrick F. Sullivan, Yi Lu, Fang Fang","doi":"10.1038/s44161-024-00488-y","DOIUrl":"10.1038/s44161-024-00488-y","url":null,"abstract":"Major depressive disorder (MDD) and cardiovascular disease (CVD) are often comorbid, resulting in excess morbidity and mortality. Here we show that CVDs share most of their genetic risk factors with MDD. Multivariate genome-wide association analysis of shared genetic liability between MDD and atherosclerotic CVD revealed seven loci and distinct patterns of tissue and brain cell-type enrichments, suggesting the involvement of the thalamus. Part of the genetic overlap was explained by shared inflammatory, metabolic and psychosocial or lifestyle risk factors. Our data indicated causal effects of genetic liability to MDD on CVD risk, but not from most CVDs to MDD, and showed that the causal effects were partly explained by metabolic and psychosocial or lifestyle factors. The distinct signature of MDD–atherosclerotic CVD comorbidity suggests an immunometabolic subtype of MDD that is more strongly associated with CVD than overall MDD. In summary, we identified biological mechanisms underlying MDD–CVD comorbidity and modifiable risk factors for prevention of CVD in individuals with MDD. Bergstedt et al. show that the effects of genetic liability to major depressive disorder can cause an increase in cardiovascular risk and that metabolic, psychological and lifestyle factors are partly responsible for this association.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00488-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425148","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}
Pub Date : 2024-06-14DOI: 10.1038/s44161-024-00492-2
Stéphanie Debette, Masafumi Ihara
Rare and common variants in HTRA1 are associated with ischemic stroke. Research now sheds light on the underlying genetic architecture and suggests a vasculopathy with a broader phenotypic spectrum. Lower HTRA1 protease activity and circulating levels both predict an increased risk of ischemic stroke and coronary artery disease.
{"title":"Redefining common and rare HTRA1 variants as risk factors for polyvascular disease","authors":"Stéphanie Debette, Masafumi Ihara","doi":"10.1038/s44161-024-00492-2","DOIUrl":"10.1038/s44161-024-00492-2","url":null,"abstract":"Rare and common variants in HTRA1 are associated with ischemic stroke. Research now sheds light on the underlying genetic architecture and suggests a vasculopathy with a broader phenotypic spectrum. Lower HTRA1 protease activity and circulating levels both predict an increased risk of ischemic stroke and coronary artery disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141343513","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}
Pub Date : 2024-06-14DOI: 10.1038/s44161-024-00493-1
Lingling Zhang, Jacob Elkahal, Tianzhen Wang, Racheli Rimmer, Alexander Genzelinakh, Elad Bassat, Jingkui Wang, Dahlia Perez, David Kain, Daria Lendengolts, Roni Winkler, Hanna Bueno-levy, Kfir Baruch Umansky, David Mishaly, Avraham Shakked, Shoval Miyara, Avital Sarusi-Portuguez, Naomi Goldfinger, Amir Prior, David Morgenstern, Yishai Levin, Yoseph Addadi, Baoguo Li, Varda Rotter, Uriel Katz, Elly M. Tanaka, Valery Krizhanovsky, Rachel Sarig, Eldad Tzahor
Senescence plays a key role in various physiological and pathological processes. We reported that injury-induced transient senescence correlates with heart regeneration, yet the multi-omics profile and molecular underpinnings of regenerative senescence remain obscure. Using proteomics and single-cell RNA sequencing, here we report the regenerative senescence multi-omic signature in the adult mouse heart and establish its role in neonatal heart regeneration and agrin-mediated cardiac repair in adult mice. We identified early growth response protein 1 (Egr1) as a regulator of regenerative senescence in both models. In the neonatal heart, Egr1 facilitates angiogenesis and cardiomyocyte proliferation. In adult hearts, agrin-induced senescence and repair require Egr1, activated by the integrin–FAK–ERK–Akt1 axis in cardiac fibroblasts. We also identified cathepsins as injury-induced senescence-associated secretory phenotype components that promote extracellular matrix degradation and potentially assist in reducing fibrosis. Altogether, we uncovered the molecular signature and functional benefits of regenerative senescence during heart regeneration, with Egr1 orchestrating the process. Zhang et al. show that Egr1 regulates transient senescence during neonatal heart regeneration and upon agrin-mediated cardiac repair in adult mice, acting downstream of the integrin–FAK–ERK–Akt1 axis in cardiac fibroblasts.
{"title":"Egr1 regulates regenerative senescence and cardiac repair","authors":"Lingling Zhang, Jacob Elkahal, Tianzhen Wang, Racheli Rimmer, Alexander Genzelinakh, Elad Bassat, Jingkui Wang, Dahlia Perez, David Kain, Daria Lendengolts, Roni Winkler, Hanna Bueno-levy, Kfir Baruch Umansky, David Mishaly, Avraham Shakked, Shoval Miyara, Avital Sarusi-Portuguez, Naomi Goldfinger, Amir Prior, David Morgenstern, Yishai Levin, Yoseph Addadi, Baoguo Li, Varda Rotter, Uriel Katz, Elly M. Tanaka, Valery Krizhanovsky, Rachel Sarig, Eldad Tzahor","doi":"10.1038/s44161-024-00493-1","DOIUrl":"10.1038/s44161-024-00493-1","url":null,"abstract":"Senescence plays a key role in various physiological and pathological processes. We reported that injury-induced transient senescence correlates with heart regeneration, yet the multi-omics profile and molecular underpinnings of regenerative senescence remain obscure. Using proteomics and single-cell RNA sequencing, here we report the regenerative senescence multi-omic signature in the adult mouse heart and establish its role in neonatal heart regeneration and agrin-mediated cardiac repair in adult mice. We identified early growth response protein 1 (Egr1) as a regulator of regenerative senescence in both models. In the neonatal heart, Egr1 facilitates angiogenesis and cardiomyocyte proliferation. In adult hearts, agrin-induced senescence and repair require Egr1, activated by the integrin–FAK–ERK–Akt1 axis in cardiac fibroblasts. We also identified cathepsins as injury-induced senescence-associated secretory phenotype components that promote extracellular matrix degradation and potentially assist in reducing fibrosis. Altogether, we uncovered the molecular signature and functional benefits of regenerative senescence during heart regeneration, with Egr1 orchestrating the process. Zhang et al. show that Egr1 regulates transient senescence during neonatal heart regeneration and upon agrin-mediated cardiac repair in adult mice, acting downstream of the integrin–FAK–ERK–Akt1 axis in cardiac fibroblasts.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141344256","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}
Pub Date : 2024-06-14DOI: 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
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.
{"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":null,"pages":null},"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}
Liver sinusoidal endothelial cells have small pores called fenestrae that allow bidirectional exchange of substrates such as lipids between hepatocytes and blood. New work reveals molecular pathways linking hyperlipidemia to these cells’ loss of fenestrae as a starting point for metabolic dysfunction-associated steatotic liver disease.
{"title":"Loss of fenestrae in liver sinusoidal endothelial cells contributes to MASLD","authors":"Nadia Ciriaci, Pierre-Emmanuel Rautou, Johanne Poisson","doi":"10.1038/s44161-024-00490-4","DOIUrl":"10.1038/s44161-024-00490-4","url":null,"abstract":"Liver sinusoidal endothelial cells have small pores called fenestrae that allow bidirectional exchange of substrates such as lipids between hepatocytes and blood. New work reveals molecular pathways linking hyperlipidemia to these cells’ loss of fenestrae as a starting point for metabolic dysfunction-associated steatotic liver disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141344582","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}
Pub Date : 2024-06-12DOI: 10.1038/s44161-024-00482-4
Randall S. Carpenter, Maria Maryanovich
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.
{"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":null,"pages":null},"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}
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