Pub Date : 2026-01-23DOI: 10.1016/j.jacbts.2025.101459
Binbin Wu PhD , Jack C.H. Chen MSc , Chloe H.Y. Ma MSc , Maxwell Kwok PhD , Valerie T. Chan , Chun C. Sung PhD , Yi Song PhD , Tao Zhang PhD , Hin S. Lam BSc , Fang Meng MSc , Yonghao Liang PhD , Chantelle Tsoi BSc , Ruixia Deng PhD , Stephen K.W. Tsui PhD , Kam T. Leung PhD , Chi C. Wang PhD , Godfrey C.F. Chan MD , Kenneth R. Boheler PhD , Kenny K.K. Chung PhD , Ellen N. Poon PhD
Doxorubicin is effective against cancer but can cause doxorubicin-induced cardiotoxicity (DCT). Drug discovery efforts against DCT are hampered by the need to balance cardioprotection and cancer control. This study demonstrates that ICG-001 suppressed DCT in patient-derived human induced pluripotent stem cell–derived cardiomyocytes in vitro and in mice in vivo, comparable to conventional treatment, dexrazoxane. Unlike dexrazoxane, ICG-001 was cytotoxic to cancer cells. Mechanistically, ICG-001 protected the mitochondria in cardiomyocytes via DPR1 inhibition, but suppressed cancer by repressing Wnt signaling. These dual mechanisms underscore the potential of ICG-001 as an adjunct treatment to doxorubicin to improve its safety and efficacy.
{"title":"ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity","authors":"Binbin Wu PhD , Jack C.H. Chen MSc , Chloe H.Y. Ma MSc , Maxwell Kwok PhD , Valerie T. Chan , Chun C. Sung PhD , Yi Song PhD , Tao Zhang PhD , Hin S. Lam BSc , Fang Meng MSc , Yonghao Liang PhD , Chantelle Tsoi BSc , Ruixia Deng PhD , Stephen K.W. Tsui PhD , Kam T. Leung PhD , Chi C. Wang PhD , Godfrey C.F. Chan MD , Kenneth R. Boheler PhD , Kenny K.K. Chung PhD , Ellen N. Poon PhD","doi":"10.1016/j.jacbts.2025.101459","DOIUrl":"10.1016/j.jacbts.2025.101459","url":null,"abstract":"<div><div>Doxorubicin is effective against cancer but can cause doxorubicin-induced cardiotoxicity (DCT). Drug discovery efforts against DCT are hampered by the need to balance cardioprotection and cancer control. This study demonstrates that ICG-001 suppressed DCT in patient-derived human induced pluripotent stem cell–derived cardiomyocytes in vitro and in mice in vivo, comparable to conventional treatment, dexrazoxane. Unlike dexrazoxane, ICG-001 was cytotoxic to cancer cells. Mechanistically, ICG-001 protected the mitochondria in cardiomyocytes via DPR1 inhibition, but suppressed cancer by repressing Wnt signaling. These dual mechanisms underscore the potential of ICG-001 as an adjunct treatment to doxorubicin to improve its safety and efficacy.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101459"},"PeriodicalIF":8.4,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035315","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 : 2026-01-20DOI: 10.1016/j.jacbts.2025.101468
Maryam Anwar PhD , Moumita Sarkar PhD , Kerrie Ford PhD , Gianni D. Angelini MD , Prakash P. Punjabi MD, PhD , Yingshu Guan MSc , Abas Laftah PhD , Aránzazu Chamorro-Jorganes PhD , Jiahui Ji PhD , Prashant K. Srivastava PhD , Enrico Petretto PhD , Costanza Emanueli PhD
Therapies promoting microvascular flow and endothelial repair require effective identification of new targets in ischemic heart disease (IHD). The aim of this study was to unravel and functionally investigate circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) networks in endothelial cells in the context of IHD and type 2 diabetes mellitus (T2DM). We performed RNA sequencing on left ventricle biopsies from patients with IHD, IHD and T2DM, and non-IHD. Next, we created circRNA-miRNA-mRNA networks and mechanistically investigated the top circRNA-miRNA sponging interactions in endothelial cells. We found that circNPHP1 promotes angiogenesis via sponging of miR-221-3p and regulates its downstream target genes, VEGFA and BCL2, in IHD and T2DM.
{"title":"Human Left Ventricle circRNA-miRNA-mRNA Network Analyses Reveal a Novel Proangiogenic Role for circNPHP1 Under Ischemic Conditions","authors":"Maryam Anwar PhD , Moumita Sarkar PhD , Kerrie Ford PhD , Gianni D. Angelini MD , Prakash P. Punjabi MD, PhD , Yingshu Guan MSc , Abas Laftah PhD , Aránzazu Chamorro-Jorganes PhD , Jiahui Ji PhD , Prashant K. Srivastava PhD , Enrico Petretto PhD , Costanza Emanueli PhD","doi":"10.1016/j.jacbts.2025.101468","DOIUrl":"10.1016/j.jacbts.2025.101468","url":null,"abstract":"<div><div>Therapies promoting microvascular flow and endothelial repair require effective identification of new targets in ischemic heart disease (IHD). The aim of this study was to unravel and functionally investigate circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) networks in endothelial cells in the context of IHD and type 2 diabetes mellitus (T2DM). We performed RNA sequencing on left ventricle biopsies from patients with IHD, IHD and T2DM, and non-IHD. Next, we created circRNA-miRNA-mRNA networks and mechanistically investigated the top circRNA-miRNA sponging interactions in endothelial cells. We found that circNPHP1 promotes angiogenesis via sponging of miR-221-3p and regulates its downstream target genes, VEGFA and BCL2, in IHD and T2DM.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101468"},"PeriodicalIF":8.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018514","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 : 2026-01-15DOI: 10.1016/j.jacbts.2025.101452
Marie E. Jost MD , Moyra Schweizer MSc , Philipp Henning PhD , Christian Gorzelanny PhD , Moritz Lehners PhD , Bernhard Ellinger PhD , Javier Boix-Campos MSc , Johan-Moritz Kux (Research technician) , Shubhangi Singh PhD , Alexandra Fachinger PhD , Karla Martinez Pomier PhD , Bryan VanSchouwen PhD , Anja M. Billing PhD , Doreen Biedenweg (Research technician) , Michaela Schweizer PhD , Saskia Siegel (Research technician) , Rudolph Reimer PhD , Mona Brandt MSc , Laura Priesmeier MD , Ulrike Fuchs MSc , Friederike Cuello PhD
Aortic dissection can strike without warning. Whereas the condition is typically linked to aging and chronic hypertension, rare genetic variants emerge as silent culprits. One variant, V219I in PRKG1, has been found in patients with aortic aneurysms despite near-normal aortic diameters. Vascular smooth muscle cells expressing the V219I variant were larger, more deformable, and showed aberrant actin cytoskeleton dynamics. They exhibited altered extracellular matrix signaling and weakened structural integrity, highlighting a shift toward increased tissue elasticity as the causal molecular pathomechanism. These findings offer a mechanistic model for how PRKG1 variants predispose to aortic dissection.
{"title":"Activating PRKG1 Variant Enhances Smooth Muscle Cell Deformability To Cause Aortopathy","authors":"Marie E. Jost MD , Moyra Schweizer MSc , Philipp Henning PhD , Christian Gorzelanny PhD , Moritz Lehners PhD , Bernhard Ellinger PhD , Javier Boix-Campos MSc , Johan-Moritz Kux (Research technician) , Shubhangi Singh PhD , Alexandra Fachinger PhD , Karla Martinez Pomier PhD , Bryan VanSchouwen PhD , Anja M. Billing PhD , Doreen Biedenweg (Research technician) , Michaela Schweizer PhD , Saskia Siegel (Research technician) , Rudolph Reimer PhD , Mona Brandt MSc , Laura Priesmeier MD , Ulrike Fuchs MSc , Friederike Cuello PhD","doi":"10.1016/j.jacbts.2025.101452","DOIUrl":"10.1016/j.jacbts.2025.101452","url":null,"abstract":"<div><div>Aortic dissection can strike without warning. Whereas the condition is typically linked to aging and chronic hypertension, rare genetic variants emerge as silent culprits. One variant, V219I in <em>PRKG1</em>, has been found in patients with aortic aneurysms despite near-normal aortic diameters. Vascular smooth muscle cells expressing the V219I variant were larger, more deformable, and showed aberrant actin cytoskeleton dynamics. They exhibited altered extracellular matrix signaling and weakened structural integrity, highlighting a shift toward increased tissue elasticity as the causal molecular pathomechanism. These findings offer a mechanistic model for how <em>PRKG1</em> variants predispose to aortic dissection.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101452"},"PeriodicalIF":8.4,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979628","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 : 2026-01-13DOI: 10.1016/j.jacbts.2025.101455
Kaelin A. Akins PhD , Anooj Arkatkar BS , Michael A. Flinn PhD , Natalie Sandor , Alexandra L. Purdy PhD , Annabelle L. Brusacoram BS , Samantha K. Swift PhD , Sydney Buday , Priyanka Choudhury PhD , Miao Cui PhD , Brian L. Lin PhD , Caitlin C. O’Meara PhD , Michaela Patterson PhD
Runx1 is strongly induced in the heart after acute injury and in chronic disease settings. Its expression negatively correlates with outcomes, and past work demonstrates a protective effect when Runx1 is inhibited through a variety of experimental means. We sought to establish which Runx1-expressing cell type(s) are responsible for the adverse remodeling phenotypes observed upon its induction. Using distinct Cre drivers, we ablated Runx1 from cardiomyocytes and fibroblasts. Following experimental myocardial infarction, we established that loss of Runx1 in fibroblasts, but not cardiomyocytes, is able to protect from adverse remodeling.
{"title":"Runx1 in Postn-Expressing Fibroblasts But Not Cardiomyocytes Exacerbates Adverse Cardiac Remodeling Post Myocardial Infarction","authors":"Kaelin A. Akins PhD , Anooj Arkatkar BS , Michael A. Flinn PhD , Natalie Sandor , Alexandra L. Purdy PhD , Annabelle L. Brusacoram BS , Samantha K. Swift PhD , Sydney Buday , Priyanka Choudhury PhD , Miao Cui PhD , Brian L. Lin PhD , Caitlin C. O’Meara PhD , Michaela Patterson PhD","doi":"10.1016/j.jacbts.2025.101455","DOIUrl":"10.1016/j.jacbts.2025.101455","url":null,"abstract":"<div><div>Runx1 is strongly induced in the heart after acute injury and in chronic disease settings. Its expression negatively correlates with outcomes, and past work demonstrates a protective effect when Runx1 is inhibited through a variety of experimental means. We sought to establish which Runx1-expressing cell type(s) are responsible for the adverse remodeling phenotypes observed upon its induction. Using distinct Cre drivers, we ablated Runx1 from cardiomyocytes and fibroblasts. Following experimental myocardial infarction, we established that loss of Runx1 in fibroblasts, but not cardiomyocytes, is able to protect from adverse remodeling.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101455"},"PeriodicalIF":8.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979627","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 : 2026-01-12DOI: 10.1016/j.jacbts.2025.101458
Anna Joachimbauer MD , Nadine Cadosch MSc , Cristina Gil-Cruz PhD , Christian Perez-Shibayama PhD , Kira Frischmann MSc , Emily Payne MD , Isabella Hanka MD , Micha T. Maeder MD, PhD , Hans Rickli MD , Felix C. Tanner MD , Frank Ruschitzka MD , Burkhard Ludewig DVM , Dörthe Schmidt MD, PhD
Echocardiographic imaging mirrors the immunopathological processes underlying the progression from acute myocarditis to inflammatory cardiomyopathy. T cell–mediated myocardial inflammation and edematous swelling in subepicardial regions at disease onset is followed by smoldering low-level myocardial inflammation or increasing cardiomyocyte loss and fibrotic remodeling. The resulting decline of cardiac function in the progressive disease is reflected and best predicted by impaired echocardiographic strain.
{"title":"Cardiopathogenic T Cells Govern Progression and Functional Remodeling in Inflammatory Cardiomyopathy and Chronic Myocarditis","authors":"Anna Joachimbauer MD , Nadine Cadosch MSc , Cristina Gil-Cruz PhD , Christian Perez-Shibayama PhD , Kira Frischmann MSc , Emily Payne MD , Isabella Hanka MD , Micha T. Maeder MD, PhD , Hans Rickli MD , Felix C. Tanner MD , Frank Ruschitzka MD , Burkhard Ludewig DVM , Dörthe Schmidt MD, PhD","doi":"10.1016/j.jacbts.2025.101458","DOIUrl":"10.1016/j.jacbts.2025.101458","url":null,"abstract":"<div><div>Echocardiographic imaging mirrors the immunopathological processes underlying the progression from acute myocarditis to inflammatory cardiomyopathy. T cell–mediated myocardial inflammation and edematous swelling in subepicardial regions at disease onset is followed by smoldering low-level myocardial inflammation or increasing cardiomyocyte loss and fibrotic remodeling. The resulting decline of cardiac function in the progressive disease is reflected and best predicted by impaired echocardiographic strain.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101458"},"PeriodicalIF":8.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966251","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 : 2026-01-09DOI: 10.1016/j.jacbts.2025.101454
Sandeep Basu PhD , Andrea Nathalie Rosas Diaz MD , Jose Max Narvaez-Paliza MD , Casie Curtin BS , Shreya Kurella BS , Monica Urias BA , Luis More Verde MD , Jaymin M. Patel MD , Aarti Asnani MD
Selective estrogen receptor degraders (SERDs) are emerging therapies for estrogen receptor-positive (ER+) breast cancer. However, certain oral SERDs, including giredestrant and camizestrant, have been associated with bradycardia in clinical trials. To elucidate the underlying molecular mechanism, we used chemical biology and genetic approaches in a zebrafish model of SERD-induced bradycardia. Giredestrant and camizestrant induced significant bradycardia in wild-type zebrafish embryos, whereas fulvestrant and amcenestrant (SERDs that do not induce bradycardia in patients) did not alter heart rate. Cotreatment with ER agonists rescued bradycardia, suggesting an ER-mediated mechanism. Mutations in gper, esr2a, and esr2b did not confer resistance to SERD-induced bradycardia, whereas esr1 mutant embryos were protected. These findings demonstrate that SERD-associated bradycardia is mediated through Esr1 signaling, supporting an on-target adverse effect.
{"title":"Selective Estrogen Receptor Degraders Induce Bradycardia by Modulating Nuclear Estrogen Signaling","authors":"Sandeep Basu PhD , Andrea Nathalie Rosas Diaz MD , Jose Max Narvaez-Paliza MD , Casie Curtin BS , Shreya Kurella BS , Monica Urias BA , Luis More Verde MD , Jaymin M. Patel MD , Aarti Asnani MD","doi":"10.1016/j.jacbts.2025.101454","DOIUrl":"10.1016/j.jacbts.2025.101454","url":null,"abstract":"<div><div>Selective estrogen receptor degraders (SERDs) are emerging therapies for estrogen receptor-positive (ER+) breast cancer. However, certain oral SERDs, including giredestrant and camizestrant, have been associated with bradycardia in clinical trials. To elucidate the underlying molecular mechanism, we used chemical biology and genetic approaches in a zebrafish model of SERD-induced bradycardia. Giredestrant and camizestrant induced significant bradycardia in wild-type zebrafish embryos, whereas fulvestrant and amcenestrant (SERDs that do not induce bradycardia in patients) did not alter heart rate. Cotreatment with ER agonists rescued bradycardia, suggesting an ER-mediated mechanism. Mutations in <em>gper</em>, <em>esr2a</em>, and <em>esr2b</em> did not confer resistance to SERD-induced bradycardia, whereas <em>esr1</em> mutant embryos were protected. These findings demonstrate that SERD-associated bradycardia is mediated through Esr1 signaling, supporting an on-target adverse effect.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101454"},"PeriodicalIF":8.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923704","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 : 2026-01-06DOI: 10.1016/j.jacbts.2025.101457
Pranav Sharma MD , Renae Judy MS , Shuai Yuan PhD , Corry Gellatly PhD , Katie L. Saxby PhD , Daniel J. Rader MD , Matthew J. Bown MD , Michael G. Levin MD , Scott M. Damrauer MD
Lp(a) is a genetically determined lipoprotein targeted by emerging therapies. In a UK Biobank analysis (1,026 abdominal aortic aneurysm [AAA] cases, 469,989 controls), elevated Lp(a) was associated with increased risk of AAA, including at clinically relevant thresholds while controlling for traditional risk factors, including ApoB. Multivariable Mendelian randomization confirmed a causal relationship between lipoprotein(a) [Lp(a)] and AAA independent of apolipoprotein B. These findings support Lp(a) as a modifiable risk factor and potential therapeutic target for AAA, a condition with limited medical treatment options. AAA should be considered as an outcome in future clinical trials of Lp(a)-lowering therapies.
{"title":"Lipoprotein(a) Is Associated With Increased Risk of Abdominal Aortic Aneurysm","authors":"Pranav Sharma MD , Renae Judy MS , Shuai Yuan PhD , Corry Gellatly PhD , Katie L. Saxby PhD , Daniel J. Rader MD , Matthew J. Bown MD , Michael G. Levin MD , Scott M. Damrauer MD","doi":"10.1016/j.jacbts.2025.101457","DOIUrl":"10.1016/j.jacbts.2025.101457","url":null,"abstract":"<div><div>Lp(a) is a genetically determined lipoprotein targeted by emerging therapies. In a UK Biobank analysis (1,026 abdominal aortic aneurysm [AAA] cases, 469,989 controls), elevated Lp(a) was associated with increased risk of AAA, including at clinically relevant thresholds while controlling for traditional risk factors, including ApoB. Multivariable Mendelian randomization confirmed a causal relationship between lipoprotein(a) [Lp(a)] and AAA independent of apolipoprotein B. These findings support Lp(a) as a modifiable risk factor and potential therapeutic target for AAA, a condition with limited medical treatment options. AAA should be considered as an outcome in future clinical trials of Lp(a)-lowering therapies.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101457"},"PeriodicalIF":8.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145904231","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 : 2026-01-01DOI: 10.1016/j.jacbts.2025.101389
Gopika SenthilKumar PhD , Zachary Zirgibel BA , Maria J. Jaramillo-Torres MD , Rachel H. Limpert BS , Katie E. Cohen MD , Carolyn Shult BA , Brian Lindemer BS , Henry Bordas-Murphy BS , Callisia N. Clarke MD, MS , Julie K. Freed MD, PhD
Microvascular endothelial dysfunction strongly predicts poor cardiovascular outcomes, and recent studies have indicated that chronic estrogen treatment promotes endothelial dysfunction in isolated human microvessels. Here, using a translational approach, we demonstrate that sphingolipids are a critical component of estrogen signaling within the human microvascular endothelium. We provide evidence that the stark differences in how estrogen influences the microvascular endothelium are both time- and sex-dependent. This work adds mechanistic insight regarding the complexity and often contradictory relationship between estrogen and cardiovascular risk in humans.
{"title":"Estrogen Influences Human Microvascular Endothelial Function Via Sex-Specific Regulation of Sphingolipids","authors":"Gopika SenthilKumar PhD , Zachary Zirgibel BA , Maria J. Jaramillo-Torres MD , Rachel H. Limpert BS , Katie E. Cohen MD , Carolyn Shult BA , Brian Lindemer BS , Henry Bordas-Murphy BS , Callisia N. Clarke MD, MS , Julie K. Freed MD, PhD","doi":"10.1016/j.jacbts.2025.101389","DOIUrl":"10.1016/j.jacbts.2025.101389","url":null,"abstract":"<div><div>Microvascular endothelial dysfunction strongly predicts poor cardiovascular outcomes, and recent studies have indicated that chronic estrogen treatment promotes endothelial dysfunction in isolated human microvessels. Here, using a translational approach, we demonstrate that sphingolipids are a critical component of estrogen signaling within the human microvascular endothelium. We provide evidence that the stark differences in how estrogen influences the microvascular endothelium are both time- and sex-dependent. This work adds mechanistic insight regarding the complexity and often contradictory relationship between estrogen and cardiovascular risk in humans.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 1","pages":"Article 101389"},"PeriodicalIF":8.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372808","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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