Circulation research最新文献

{"title":"Isolevuglandins Modulate Histone H1 in Myeloid Cells in Salt-Sensitive Hypertension.","authors":"Jeremiah M Afolabi,Mohammad Saleem,Annet Kirabo,Ashley L Mutchler","doi":"10.1161/circresaha.125.326808","DOIUrl":"https://doi.org/10.1161/circresaha.125.326808","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"5 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189311","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":"Human Multi-Organoid Platform to Model Immune Dynamics in Cardiac Injury and Disease.","authors":"Jasmeet S Reyat, Yuqi Shen, Gowsihan Poologasundarampillai, Amirpasha Moetazedian, Julie Rayes, Abdullah O Khan","doi":"10.1161/CIRCRESAHA.125.326823","DOIUrl":"10.1161/CIRCRESAHA.125.326823","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"1133-1136"},"PeriodicalIF":16.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944695","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":"Meet the First Authors.","authors":"","doi":"10.1161/RES.0000000000000733","DOIUrl":"https://doi.org/10.1161/RES.0000000000000733","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"137 8","pages":"1049-1050"},"PeriodicalIF":16.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148174","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":"Calcium Oscillations Within Juxtaglomerular Cell Clusters Control Renin Release.","authors":"Hiroki Yamaguchi, Nick A Guagliardo, Laura A Bell, Manako Yamaguchi, Daisuke Matsuoka, Fang Xu, Jason P Smith, Mohamed Diagne, Sophie Condron, Lucas F Almeida, Silvia Medrano, Paula Q Barrett, Edward H Nieh, R Ariel Gomez, Maria Luisa S Sequeira-Lopez","doi":"10.1161/CIRCRESAHA.125.326541","DOIUrl":"10.1161/CIRCRESAHA.125.326541","url":null,"abstract":"<p><strong>Background: </strong>Juxtaglomerular cells are sensors that control blood pressure and fluid-electrolyte homeostasis. They are arranged as clusters at the tip of each afferent arteriole. In response to decreased blood pressure or extracellular fluid volume, juxtaglomerular cells secrete renin, initiating an enzymatic cascade that culminates in the production of Ang II (angiotensin II), a potent vasoconstrictor that restores blood pressure and fluid-electrolyte homeostasis. In turn, Ang II exerts negative feedback on renin release commensurate with increased intracellular Ca<sup>2+</sup>, preventing excessive circulating renin and hypertension. However, within their native structural organization, the intricacies of intracellular Ca<sup>2+</sup> signaling dynamics and their sources remain uncharacterized.</p><p><strong>Methods: </strong>We generated mice expressing the juxtaglomerular cell-specific genetically encoded Ca<sup>2+</sup> indicator (GCaMP6f) to investigate Ca<sup>2+</sup> dynamics within juxtaglomerular cell clusters ex vivo and in vivo. For ex vivo Ca<sup>2+</sup> imaging, acutely prepared kidney slices were perfused continuously with a buffer containing variable Ca<sup>2+</sup> and Ang II concentrations ±Ca<sup>2+</sup> channel inhibitors. For in vivo Ca<sup>2+</sup> image capture, native mouse kidneys were imaged in situ using multiphoton microscopy with and without Ang II and Ang II type-1 receptor blocker losartan administration. ELISA measurements determined acute renin secretion ex vivo and in vivo.</p><p><strong>Results: </strong>Ex vivo Ca<sup>2+</sup> imaging revealed that juxtaglomerular cell clusters exhibit robust and coordinated intracellular oscillatory signals with cell-cell propagation following Ang II stimulation. Ang II dose-dependently induced stereotypical burst patterns characterized by consecutive Ca<sup>2+</sup> spikes, which inversely correlated with renin secretion. Pharmacological channel inhibition identified key sources of these oscillations: endoplasmic reticulum Ca<sup>2+</sup> storage and release, extracellular Ca<sup>2+</sup> uptake via store-operated ORAI (Ca<sup>2+</sup>-selective plasma membrane channels involved in store-operated Ca<sup>2+</sup> entry) Ca<sup>2+</sup> channels, and intercellular communication through gap junctions. Blocking ORAI channels and gap junctions reduced Ang II inhibitory effect on renin secretion. In vivo Ca<sup>2+</sup> imaging demonstrated robust intracellular and intercellular Ca<sup>2+</sup> oscillations within juxtaglomerular cell clusters under physiological conditions, exhibiting spike patterns consistent with those measured in ex vivo preparations. Ang II administration enhanced the Ca<sup>2+</sup> oscillatory signals and suppressed acute renin secretion, whereas losartan produced inverse effects in vivo.</p><p><strong>Conclusions: </strong>Ang II elicits coordinated intracellular and intercellular Ca<sup>2+</sup> oscillations within juxtaglomerular cell","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"1051-1068"},"PeriodicalIF":16.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945051","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":"Correction to: Cardiac Ketone Body Oxidation Enhances Exercise Performance.","authors":"Kara R Gouwens, Ernesto Pena Calderin, Jada Okhiria, Daniel C Nguyen, Emily B Schulman-Geltzer, Yania Martinez-Ondaro, Maleesha De Silva, Helen E Collins, Yibing Nong, Sophia M Sears, Matthew A Nystoriak, Bradford G Hill","doi":"10.1161/RES.0000000000000732","DOIUrl":"https://doi.org/10.1161/RES.0000000000000732","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"137 8","pages":"e176"},"PeriodicalIF":16.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148203","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":"Single-Short Partial Reprogramming of the Endothelial Cells Decreases Blood Pressure via Attenuation of EndMT in Hypertensive Mice.","authors":"Laena Pernomian, Emily W Waigi, Vi Nguyen, Ahmed D Mohammed, Tiago J Costa, Milene T Fontes, Jason L Kubinak, Andrew V Aitken, Vinicia Campana Biancardi, Kamryn Gleason, Tarek Shazly, David A Sinclair, Cameron G McCarthy, Yunguan Wang, Wenbin Tan, Camilla Ferreira Wenceslau","doi":"10.1161/CIRCRESAHA.124.324909","DOIUrl":"10.1161/CIRCRESAHA.124.324909","url":null,"abstract":"<p><strong>Background: </strong>Small artery remodeling and endothelial dysfunction are hallmarks of hypertension. Evidence supports a likely causal association between cardiovascular diseases and endothelial-to-mesenchymal transition (EndMT), a cellular transdifferentiation process in which endothelial cells (ECs) partially lose their identity and acquire mesenchymal phenotypes. EC reprogramming represents an innovative strategy in regenerative medicine to prevent deleterious effects induced by cardiovascular diseases.</p><p><strong>Methods: </strong>Using partial reprogramming of ECs, via overexpression of Oct-3/4-Sox-2-Klf-4 (OSK) transcription factors, we aimed to bring ECs back to a youthful phenotype in hypertension. Primary ECs were infected with lentiviral vectors (LVs) containing the specific EC promoter Cdh5 (cadherin-5) and the reporter EGFP (enhanced green fluorescent protein) with empty vector (LV control) or LV with Oct-3/4-Sox-2-Klf-4. Confocal microscopy and Western blotting analysis were used to confirm OSK overexpression. Cellular migration, senescence, and apoptosis were evaluated. Human aortic ECs from normotensive patients and patients with hypertension were analyzed after OSK treatments for eNOS (endothelial nitric oxide synthase), nitric oxide (NO), and genetic profile. Male and female normotensive (BPN/3J or blood pressure normal mouse strain) and hypertensive (BPH/2J or blood pressure high mouse strain) mice were treated with LV control or LV with Oct-3/4-Sox-2-Klf-4 and evaluated 10 days post-infection. The blood pressure, cardiac function, vascular reactivity of small arteries, and EndMT inhibition were analyzed.</p><p><strong>Results: </strong>OSK overexpression induced partial EC reprogramming in vitro, and these cells had lower migratory capability. OSK treatment of BPH/2J mice reduced blood pressure and resistance arteries hypercontractility, via the attenuation of endothelial-to-mesenchymal transition and elastin breaks. EGFP was detected in vivo in the prefrontal cortex. OSK-treated hypertensive human aortic ECs showed high eNOS activation and NO production, with low reactive oxygen species (ROS) formation. Single-cell RNA analysis showed that OSK alleviated EC senescence and EndMT, restoring their phenotypes in human aortic ECs from patients with hypertension.</p><p><strong>Conclusions: </strong>Overall, these data indicate that OSK treatment and EC reprogramming can decrease blood pressure and reverse hypertension-induced vascular damage.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"1092-1113"},"PeriodicalIF":16.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944868","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":"Septin4 Regulates Cardiac Fibrosis After Pressure Overload.","authors":"Doğacan Yücel, Natalia Ferreira de Araujo, Fernando Souza-Neto, Calvin Smith, Wei-Han Lin, Andrea A Torniainen, Mikayla L Hall, DeWayne Townsend, Brenda M Ogle, Jop H van Berlo","doi":"10.1161/CIRCRESAHA.125.326758","DOIUrl":"10.1161/CIRCRESAHA.125.326758","url":null,"abstract":"<p><strong>Background: </strong>In response to cardiac injury the mammalian heart undergoes ventricular remodeling to maintain cardiac function. These changes are initially considered compensatory, but eventually lead to increased cardiomyocyte apoptosis, reduced cardiac function and fibrosis which are important contributors to the development of heart failure. The small GTPase Sept4 (Septin4) has previously been implicated in the regulation of regeneration and apoptosis in several organs. However, the role of Sept4 in regulating the response of the heart to stress is unknown.</p><p><strong>Methods: </strong>Ten-week-old wild-type (WT) and Sept4 knockout mice were subjected to transverse aortic constriction to induce cardiac injury. Genotype-dependent differences were investigated at baseline and at 1- and 4-week postinjury time points. To definitively establish the fibroblast-specific cardioprotective effects of Sept4, we generated a fibroblast-specific Sept4 conditional knockout model.</p><p><strong>Results: </strong>Under homeostatic conditions Sept4 knockout mice showed normal cardiac function comparable with WT controls. In response to transverse aortic constriction, WT mice developed reduced cardiac function and heart failure, accompanied by an increase in cardiomyocyte apoptosis. In contrast, knockout mice were protected against injury with maintenance of normal cardiac function and reduced levels of cardiomyocyte apoptosis. Both at baseline and after transverse aortic constriction, knockout hearts exhibited decreased levels of cardiac extracellular matrix deposition and fibrosis compared with WT controls. In support of these data, the level of myofibroblast activation was lower after injury in knockout mice. Furthermore, the knockout group showed higher levels of cardiac compliance and improved diastolic function compared with WT controls. Mechanistically, we identified reduced fibrosis development due to alterations in calcineurin-dependent signaling in fibroblasts. These results were further verified in fibroblast-specific conditional Sept4 knockout mice subjected to cardiac pressure overload.</p><p><strong>Conclusions: </strong>We identified Sept4 as an important regulator of extracellular matrix remodeling in the heart. Sept4 controls the conversion of fibroblast to myofibroblast through calcineurin-dependent mechanisms.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"1117-1132"},"PeriodicalIF":16.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079675","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":"Coming Back to Life: Resilience of Endothelium Despite the Burden of Hypertension.","authors":"Frank M Faraci","doi":"10.1161/circresaha.125.327250","DOIUrl":"https://doi.org/10.1161/circresaha.125.327250","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"41 1","pages":"1114-1116"},"PeriodicalIF":20.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140253","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":"From Tigerstedt to Calcium Oscillations: A Remarkable Journey in Renin Research.","authors":"Leonie Dreher,A H Jan Danser,Ulrich O Wenzel","doi":"10.1161/circresaha.125.327186","DOIUrl":"https://doi.org/10.1161/circresaha.125.327186","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"63 1","pages":"1069-1071"},"PeriodicalIF":20.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140159","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":"Unlocking Mitochondrial Potential: DWORF to the Rescue in Heart Failure.","authors":"Mahmoud H Elbatreek,David J Lefer","doi":"10.1161/circresaha.125.327249","DOIUrl":"https://doi.org/10.1161/circresaha.125.327249","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"100 1","pages":"1089-1091"},"PeriodicalIF":20.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140321","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}