Cardiovascular Research最新文献

{"title":"Leveraging metabolism for better outcomes in heart failure.","authors":"Yann Huey Ng, Yen Chin Koay, Francine Z Marques, David M Kaye, John F O'Sullivan","doi":"10.1093/cvr/cvae216","DOIUrl":"https://doi.org/10.1093/cvr/cvae216","url":null,"abstract":"<p><p>Whilst metabolic inflexibility and substrate constraint have been observed in heart failure for many years, their exact causal role remains controversial. In parallel, many of our fundamental assumptions about cardiac fuel use are now being challenged like never before. For example, the emergence of sodium glucose cotransporter 2 inhibitor (SGLT2i) therapy as one of the four \"pillars\" of heart failure therapy is causing a revisit of metabolism as a key mechanism and therapeutic target in heart failure. Improvements in the field of cardiac metabolomics will lead to a far more granular understanding of the mechanisms underpinning normal and abnormal human cardiac fuel use, an appreciation of drug action, and novel therapeutic strategies. Technological advances and expanding biorepositories offer exciting opportunities to elucidate the novel aspects of these metabolic mechanisms. Methodologic advances include comprehensive and accurate substrate quantitation such as metabolomics and stable-isotope fluxomics, improved access to arterio-venous blood samples across the heart to determine fuel consumption and energy conversion, high quality cardiac tissue biopsies, biochemical analytics, and informatics. Pairing these technologies with recent discoveries in epigenetic regulation, mitochondrial dynamics, and organ-microbiome metabolic crosstalk will garner critical mechanistic insights in heart failure. In this state-of-the-art review, we focus on new metabolic insights, with an eye on emerging metabolic strategies for heart failure. Our synthesis of the field will be valuable for a diverse audience with an interest in cardiac metabolism.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342269","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}

{"title":"The cardiologist in the age of artificial intelligence: what is left for us?","authors":"Thomas F Lüscher, Florian A Wenzl","doi":"10.1093/cvr/cvae171","DOIUrl":"https://doi.org/10.1093/cvr/cvae171","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388301","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}

{"title":"Renal denervation achieves its antiarrhythmic effect through attenuating macrophage activation and neuroinflammation in stellate ganglia in chronic heart failure","authors":"Wenfeng Hu, Huiyin Tu, Michael C Wadman, Yu-Long Li, Dongze Zhang","doi":"10.1093/cvr/cvae196","DOIUrl":"https://doi.org/10.1093/cvr/cvae196","url":null,"abstract":"Aims Renal denervation (RDN) is widely investigated in multiple studies of sympathetically driven cardiovascular diseases. While the therapeutic potential of RDN for ventricular arrhythmia has been reported, the mechanisms responsible for its antiarrhythmic effect are poorly understood. Our recent study showed that macrophage expansion-induced neuroinflammation in the stellate ganglion (SG) was a critical factor for cardiac sympathetic overactivation and ventricular arrhythmogenesis in chronic heart failure (CHF). This study investigates if and how RDN decreases ventricular arrhythmias by attenuating neuroinflammation in cardiac sympathetic postganglionic (CSP) neurons in CHF. Methods and Results Rat CHF was induced by surgical ligation of the left anterior descending coronary artery (LAD). At 12 weeks after LAD ligation, completed bilateral RDN was achieved by surgically cutting all the visible renal nerves around the renal artery and vein, followed by applying of 70% ethanol around the vessels. Immunofluorescence staining and Western blot data showed that expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor-α subunit (GM-CSFRα) in SGs was increased in CHF rats. RDN not only reduced CHF-elevated GM-CSF levels in kidney, serum and SGs, but also attenuated macrophage expansion and neuroinflammation in SGs from CHF rats. Using flow cytometry, we confirmed that RDN reduced the percentage of macrophages in SGs, which is pathologically increased in CHF. RDN also decreased CHF-enhanced N-type Ca2+ currents in CSP neurons and attenuated CHF-elevated cardiac sympathetic nerve activity. ECG data from 24-hour continuous telemetry recording in conscious rats revealed that RDN improved CHF-induced heterogeneity of ventricular electrical activities and reduced the duration of spontaneous ventricular tachyarrhythmias in CHF rats. Conclusions RDN alleviates cardiac sympathetic overactivation and ventricular arrhythmogenesis through attenuating GM-CSF-induced macrophage activation and neuroinflammation within SGs in CHF. This suggests that manipulation of the GM-CSF signaling pathway could be a novel strategy for achieving the antiarrhythmic effect of RDN in CHF.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"35 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321378","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}

{"title":"GDF15 antagonism limits severe heart failure and prevents cardiac cachexia.","authors":"Minoru Takaoka, John A Tadross, Ali B A K Al-Hadithi, Xiaohui Zhao, Rocío Villena-Gutiérrez, Jasper Tromp, Shazia Absar, Marcus Au, James Harrison, Anthony P Coll, Stefan J Marciniak, Debra Rimmington, Eduardo Oliver, Borja Ibáñez, Adriaan A Voors, Stephen O'Rahilly, Ziad Mallat, Jane C Goodall","doi":"10.1093/cvr/cvae214","DOIUrl":"https://doi.org/10.1093/cvr/cvae214","url":null,"abstract":"<p><strong>Aims: </strong>Heart failure and associated cachexia is an unresolved and important problem. This study aimed to determine the factors that contribute to cardiac cachexia in a new model of heart failure in mice that lack the integrated stress response (ISR) induced eIF2α phosphatase, PPP1R15A.</p><p><strong>Methods and results: </strong>Mice were irradiated and reconstituted with bone marrow cells. Mice lacking functional PPP1R15A, exhibited dilated cardiomyopathy and severe weight loss following irradiation, whilst wild-type mice were unaffected. This was associated with increased expression of Gdf15 in the heart and increased levels of GDF15 in circulation. We provide evidence that the blockade of GDF15 activity prevents cachexia and slows the progression of heart failure. We also show the relevance of GDF15 to lean mass and protein intake in patients with heart failure.</p><p><strong>Conclusion: </strong>Our data suggest that cardiac stress mediates a GDF15-dependent pathway that drives weight loss and worsens cardiac function. Blockade of GDF15 could constitute a novel therapeutic option to limit cardiac cachexia and improve clinical outcomes in patients with severe systolic heart failure.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307167","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}

{"title":"Hypoxia-responsive zinc finger E-box-binding homeobox 2 (ZEB2) regulates a network of calcium-handling genes in the injured heart.","authors":"Monika M Gladka, Arwa Kohela, Anne E de Leeuw, Bas Molenaar, Danielle Versteeg, Lieneke Kooijman, Mariska van Geldorp, Willem B van Ham, Rocco Caliandro, Jody J Haigh, Toon A B van Veen, Eva van Rooij","doi":"10.1093/cvr/cvae163","DOIUrl":"https://doi.org/10.1093/cvr/cvae163","url":null,"abstract":"<p><strong>Aims: </strong>Intracellular calcium (Ca2+) overload is known to play a critical role in the development of cardiac dysfunction. Despite the remarkable improvement in managing the progression of heart disease, developing effective therapies for heart failure (HF) remains a challenge. A better understanding of molecular mechanisms that maintain proper Ca2+ levels and contractility in the injured heart could be of therapeutic value.</p><p><strong>Methods and results: </strong>Here, we report that transcription factor zinc finger E-box-binding homeobox 2 (ZEB2) is induced by hypoxia-inducible factor 1-alpha (HIF1α) in hypoxic cardiomyocytes and regulates a network of genes involved in Ca2+ handling and contractility during ischaemic heart disease. Gain- and loss-of-function studies in genetic mouse models revealed that ZEB2 expression in cardiomyocytes is necessary and sufficient to protect the heart against ischaemia-induced diastolic dysfunction and structural remodelling. Moreover, RNA sequencing of ZEB2-overexpressing (Zeb2 cTg) hearts post-injury implicated ZEB2 in regulating numerous Ca2+-handling and contractility-related genes. Mechanistically, ZEB2 overexpression increased the phosphorylation of phospholamban at both serine-16 and threonine-17, implying enhanced activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), thereby augmenting SR Ca2+ uptake and contractility. Furthermore, we observed a decrease in the activity of Ca2+-dependent calcineurin/NFAT signalling in Zeb2 cTg hearts, which is the main driver of pathological cardiac remodelling. On a post-transcriptional level, we showed that ZEB2 expression can be regulated by the cardiomyocyte-specific microRNA-208a (miR-208a). Blocking the function of miR-208a with anti-miR-208a increased ZEB2 expression in the heart and effectively protected from the development of pathological cardiac hypertrophy.</p><p><strong>Conclusion: </strong>Together, we present ZEB2 as a central regulator of contractility and Ca2+-handling components in the mammalian heart. Further mechanistic understanding of the role of ZEB2 in regulating Ca2+ homeostasis in cardiomyocytes is an essential step towards the development of improved therapies for HF.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280710","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}

{"title":"A non-genetic model of vascular shunts informs on the cellular mechanisms of formation and resolution of arteriovenous malformations.","authors":"Marie Ouarné, Andreia Pena, Daniela Ramalho, Nadine V Conchinha, Tiago Costa, Romain Enjalbert, Ana M Figueiredo, Marta Pimentel Saraiva, Yulia Carvalho, Miguel O Bernabeu, Lenka Henao Misikova, S Paul Oh, Cláudio A Franco","doi":"10.1093/cvr/cvae160","DOIUrl":"https://doi.org/10.1093/cvr/cvae160","url":null,"abstract":"<p><strong>Aims: </strong>Arteriovenous malformations (AVMs), a disorder characterized by direct shunts between arteries and veins, are associated with genetic mutations. However, the mechanisms leading to AV shunt formation and how shunts can be reverted are poorly understood.</p><p><strong>Methods and results: </strong>Here, we report that oxygen-induced retinopathy (OIR) protocol leads to the consistent and stereotypical formation of AV shunts in non-genetically altered mice. OIR-induced AV shunts show all the canonical markers of AVMs. Genetic and pharmacological interventions demonstrated that changes in the volume of venous endothelial cells (EC)-hypertrophic venous cells-are the initiating step promoting AV shunt formation, whilst EC proliferation or migration played minor roles. Inhibition of the mTOR pathway prevents pathological increases in EC volume and significantly reduces the formation of AV shunts. Importantly, we demonstrate that ALK1 signalling cell-autonomously regulates EC volume in pro-angiogenic conditions, establishing a link with hereditary haemorrhagic telangiectasia-related AVMs. Finally, we demonstrate that a combination of EC volume control and EC migration is associated with the regression of AV shunts.</p><p><strong>Conclusion: </strong>Our findings highlight that an increase in the EC volume is the key mechanism driving the initial stages of AV shunt formation, leading to asymmetric capillary diameters. Based on our results, we propose a coherent and unifying timeline leading to the fast conversion of a capillary vessel into an AV shunt. Our data advocate for further investigation into the mechanisms regulating EC volume in health and disease as a way to identify therapeutic approaches to prevent and revert AVMs.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280609","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}

{"title":"Cardiomyocyte βII spectrin plays a critical role in maintaining cardiac function by regulating mitochondrial respiratory function.","authors":"Rongjin Yang, Banjun Ruan, Rutao Wang, Xiaomeng Zhang, Pingping Xing, Congye Li, Yunyun Zhang, Xiaoqian Chang, Haifeng Song, Shun Zhang, Huishou Zhao, Feiyu Zhang, Tao Yin, Tingting Qi, Wenjun Yan, Fuyang Zhang, Guangyu Hu, Shan Wang, Ling Tao","doi":"10.1093/cvr/cvae116","DOIUrl":"10.1093/cvr/cvae116","url":null,"abstract":"<p><strong>Aims: </strong>βII spectrin is a cytoskeletal protein known to be tightly linked to heart development and cardiovascular electrophysiology. However, the roles of βII spectrin in cardiac contractile function and pathological post-myocardial infarction remodelling remain unclear. Here, we investigated whether and how βII spectrin, the most common isoform of non-erythrocytic spectrin in cardiomyocytes, is involved in cardiac contractile function and ischaemia/reperfusion (I/R) injury.</p><p><strong>Methods and results: </strong>We observed that the levels of serum βII spectrin breakdown products (βII SBDPs) were significantly increased in patients with acute myocardial infarction (AMI). Concordantly, βII spectrin was degraded into βII SBDPs by calpain in mouse hearts after I/R injury. Using tamoxifen-inducible cardiac-specific βII spectrin knockout mice, we found that deletion of βII spectrin in the adult heart resulted in spontaneous development of cardiac contractile dysfunction, cardiac hypertrophy, and fibrosis at 5 weeks after tamoxifen treatment. Moreover, at 1 week after tamoxifen treatment, although spontaneous cardiac dysfunction in cardiac-specific βII spectrin knockout mice had not developed, deletion of βII spectrin in the heart exacerbated I/R-induced cardiomyocyte death and heart failure. Furthermore, restoration of βII spectrin expression via adenoviral small activating RNA (saRNA) delivery into the heart reduced I/R injury. Immunoprecipitation coupled with mass spectrometry (IP-LC-MS/MS) analyses and functional studies revealed that βII spectrin is indispensable for mitochondrial complex I activity and respiratory function. Mechanistically, βII spectrin promotes translocation of NADH:ubiquinone oxidoreductase 75-kDa Fe-S protein 1 (NDUFS1) from the cytosol to mitochondria by crosslinking with actin filaments (F-actin) to maintain F-actin stability.</p><p><strong>Conclusion: </strong>βII spectrin is an essential cytoskeletal element for preserving mitochondrial homeostasis and cardiac function. Defects in βII spectrin exacerbate cardiac I/R injury.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1312-1326"},"PeriodicalIF":10.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236264","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}

{"title":"How far are we from accurate sex-specific risk prediction of cardiovascular disease? One size may not fit all.","authors":"Bi Huang, Mayank Dalakoti, Gregory Y H Lip","doi":"10.1093/cvr/cvae135","DOIUrl":"10.1093/cvr/cvae135","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1237-1238"},"PeriodicalIF":10.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305458","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}

{"title":"Novel formylpeptide receptor 1/2 agonist limits hypertension-induced cardiovascular damage.","authors":"Jaideep Singh, Kristy L Jackson, Haoyun Fang, Audrey Gumanti, Bethany Claridge, Feng Shii Tang, Helen Kiriazis, Ekaterina Salimova, Alex M Parker, Cameron Nowell, Owen L Woodman, David W Greening, Rebecca H Ritchie, Geoffrey A Head, Cheng Xue Qin","doi":"10.1093/cvr/cvae103","DOIUrl":"10.1093/cvr/cvae103","url":null,"abstract":"<p><strong>Aims: </strong>Formylpeptide receptors (FPRs) play a critical role in the regulation of inflammation, an important driver of hypertension-induced end-organ damage. We have previously reported that the biased FPR small-molecule agonist, compound17b (Cmpd17b), is cardioprotective against acute, severe inflammatory insults. Here, we reveal the first compelling evidence of the therapeutic potential of this novel FPR agonist against a longer-term, sustained inflammatory insult, i.e. hypertension-induced end-organ damage. The parallels between the murine and human hypertensive proteome were also investigated.</p><p><strong>Methods and results: </strong>The hypertensive response to angiotensin II (Ang II, 0.7 mg/kg/day, s.c.) was attenuated by Cmpd17b (50 mg/kg/day, i.p.). Impairments in cardiac and vascular function assessed via echocardiography were improved by Cmpd17b in hypertensive mice. This functional improvement was accompanied by reduced cardiac and aortic fibrosis and vascular calcification. Cmpd17b also attenuated Ang II-induced increased cardiac mitochondrial complex 2 respiration. Proteomic profiling of cardiac and aortic tissues and cells, using label-free nano-liquid chromatography with high-sensitivity mass spectrometry, detected and quantified ∼6000 proteins. We report hypertension-impacted protein clusters associated with dysregulation of inflammatory, mitochondrial, and calcium responses, as well as modified networks associated with cardiovascular remodelling, contractility, and structural/cytoskeletal organization. Cmpd17b attenuated hypertension-induced dysregulation of multiple proteins in mice, and of these, ∼110 proteins were identified as similarly dysregulated in humans suffering from adverse aortic remodelling and cardiac hypertrophy.</p><p><strong>Conclusion: </strong>We have demonstrated, for the first time, that the FPR agonist Cmpd17b powerfully limits hypertension-induced end-organ damage, consistent with proteome networks, supporting development of pro-resolution FPR-based therapeutics for treatment of systemic hypertension complications.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1336-1350"},"PeriodicalIF":10.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330379","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}

{"title":"Transient stabilization of human cardiovascular progenitor cells from human pluripotent stem cells in vitro reflects stage-specific heart development in vivo.","authors":"Emiliano Bolesani, Dorothee Bornhorst, Lavanya M Iyer, Dorota Zawada, Nina Friese, Michael Morgan, Lucas Lange, David M Gonzalez, Nadine Schrode, Andreas Leffler, Julian Wunder, Annika Franke, Lika Drakhlis, Robert Sebra, Axel Schambach, Alexander Goedel, Nicole C Dubois, Gergana Dobreva, Alessandra Moretti, Laura C Zelaráyan, Salim Abdelilah-Seyfried, Robert Zweigerdt","doi":"10.1093/cvr/cvae118","DOIUrl":"10.1093/cvr/cvae118","url":null,"abstract":"<p><strong>Aims: </strong>Understanding the molecular identity of human pluripotent stem cell (hPSC)-derived cardiac progenitors and mechanisms controlling their proliferation and differentiation is valuable for developmental biology and regenerative medicine.</p><p><strong>Methods and results: </strong>Here, we show that chemical modulation of histone acetyl transferases (by IQ-1) and WNT (by CHIR99021) synergistically enables the transient and reversible block of directed cardiac differentiation progression on hPSCs. The resulting stabilized cardiovascular progenitors (SCPs) are characterized by ISL1pos/KI-67pos/NKX2-5neg expression. In the presence of the chemical inhibitors, SCPs maintain a proliferation quiescent state. Upon small molecules, removal SCPs resume proliferation and concomitant NKX2-5 up-regulation triggers cell-autonomous differentiation into cardiomyocytes. Directed differentiation of SCPs into the endothelial and smooth muscle lineages confirms their full developmental potential typical of bona fide cardiovascular progenitors. Single-cell RNA-sequencing-based transcriptional profiling of our in vitro generated human SCPs notably reflects the dynamic cellular composition of E8.25-E9.25 posterior second heart field of mouse hearts, hallmarked by nuclear receptor sub-family 2 group F member 2 expression. Investigating molecular mechanisms of SCP stabilization, we found that the cell-autonomously regulated retinoic acid and BMP signalling is governing SCP transition from quiescence towards proliferation and cell-autonomous differentiation, reminiscent of a niche-like behaviour.</p><p><strong>Conclusion: </strong>The chemically defined and reversible nature of our stabilization approach provides an unprecedented opportunity to dissect mechanisms of cardiovascular progenitors' specification and reveal their cellular and molecular properties.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1295-1311"},"PeriodicalIF":10.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247652","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}