{"title":"Lipoprotein(a) and Abdominal Aortic Aneurysm","authors":"Regent Lee DPhil (Oxon)","doi":"10.1016/j.jacbts.2026.101485","DOIUrl":"10.1016/j.jacbts.2026.101485","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101485"},"PeriodicalIF":8.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283954","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}
Douglas L. Mann MD , Arthur M. Feldman MD, PhD , Mona Fiuzat PharmD , Chrisopher M. O’Connor MD , J. David Port PhD
{"title":"Michael R. Bristow, MD, PhD","authors":"Douglas L. Mann MD , Arthur M. Feldman MD, PhD , Mona Fiuzat PharmD , Chrisopher M. O’Connor MD , J. David Port PhD","doi":"10.1016/j.jacbts.2026.101483","DOIUrl":"10.1016/j.jacbts.2026.101483","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101483"},"PeriodicalIF":8.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283921","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}
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
{"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":"2026-02-01","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}
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
{"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":"2026-02-01","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}
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
{"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":"2026-02-01","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}
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
{"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":"2026-02-01","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}
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
{"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":"2026-02-01","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}
{"title":"Myosin-Specific T Cells at the Heart of Myocardial Pathophysiology","authors":"Anna Rizakou PhD , Gustavo Campos Ramos PhD","doi":"10.1016/j.jacbts.2026.101492","DOIUrl":"10.1016/j.jacbts.2026.101492","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 2","pages":"Article 101492"},"PeriodicalIF":8.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283996","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}