Pub Date : 2025-09-01Epub Date: 2025-08-21DOI: 10.1016/j.jacbts.2025.101345
Alex M. Parker MBiomedSc , Jarmon G. Lees PhD , Andrew J. Murray PhD , Anida Velagic PhD , Shiang Y. Lim MPharm, PhD , Miles J. De Blasio PhD , Rebecca H. Ritchie PhD
A substantial component of the increasing global burden of cardiovascular disease is attributed to heart failure (HF), affecting over 64 million adults worldwide. Maladaptive mitochondrial respiratory alterations and oxidative stress are major contributors to HF development and progression, with subsequent downstream myocardial energetic impairment as a strong predictor of mortality. Current conventional therapeutic approaches, including renin-angiotensin-aldosterone system inhibition and β-adrenergic blockade, target neurohormonal aspects of HF and are effective in slowing disease progression. However, although these therapies may be associated with some improvement in myocardial energetics, they do not specifically address alterations in myocardial mitochondrial respiration or redox homeostasis. Targeting mitochondria has hence become a promising approach for more effective and tailored therapies. This review summarizes metabolic derangements that drive HF progression, with a specific focus on mitochondria. Importantly, here we address the essential knowledge gaps in the field, highlighting key translational strategies used to date, and the challenges associated with therapeutically targeting mitochondrial pathways, alongside recent developments seeking to deploy novel mitochondrial-targeted therapeutic approaches to treat HF.
{"title":"Precision Medicine","authors":"Alex M. Parker MBiomedSc , Jarmon G. Lees PhD , Andrew J. Murray PhD , Anida Velagic PhD , Shiang Y. Lim MPharm, PhD , Miles J. De Blasio PhD , Rebecca H. Ritchie PhD","doi":"10.1016/j.jacbts.2025.101345","DOIUrl":"10.1016/j.jacbts.2025.101345","url":null,"abstract":"<div><div>A substantial component of the increasing global burden of cardiovascular disease is attributed to heart failure (HF), affecting over 64 million adults worldwide. Maladaptive mitochondrial respiratory alterations and oxidative stress are major contributors to HF development and progression, with subsequent downstream myocardial energetic impairment as a strong predictor of mortality. Current conventional therapeutic approaches, including renin-angiotensin-aldosterone system inhibition and β-adrenergic blockade, target neurohormonal aspects of HF and are effective in slowing disease progression. However, although these therapies may be associated with some improvement in myocardial energetics, they do not specifically address alterations in myocardial mitochondrial respiration or redox homeostasis. Targeting mitochondria has hence become a promising approach for more effective and tailored therapies. This review summarizes metabolic derangements that drive HF progression, with a specific focus on mitochondria. Importantly, here we address the essential knowledge gaps in the field, highlighting key translational strategies used to date, and the challenges associated with therapeutically targeting mitochondrial pathways, alongside recent developments seeking to deploy novel mitochondrial-targeted therapeutic approaches to treat HF.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101345"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880129","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 : 2025-09-01Epub Date: 2025-08-05DOI: 10.1016/j.jacbts.2025.101355
Constance C.F.M.J. Baaten PhD , Julia Wollenhaupt PhD , Tobias M. Henning MD , Sonja Vondenhoff MS , Jonas R. Schröer MD , Eleni Stamellou MD, PhD, MS , Turgay Saritas MD, PhD , Berkan Kurt MD , Leonard Boger MD , Alessandra Antwerpen , Juliane Hermann PhD , Magdolna Nagy PhD , Marieke Sternkopf PhD , Eva Miriam Buhl PhD , Ute Raffetseder PhD , Paola E.J. van der Meijden PhD , Marijke J.E. Kuijpers PhD , Henri M.H. Spronk PhD , Stefan J. Schunk MD , Joachim Jankowski PhD , Heidi Noels PhD
Patients with chronic kidney disease (CKD) are at increased risk of thrombotic and hemorrhagic complications. Findings on platelet defects in CKD are conflicting. Therefore, we examined platelet function in CKD stage 3 to 5 dialysis patients without antithrombotic therapy, in CKD5D/hemodialysis patients on acetylsalicylic acid (ASA) as well as in a CKD mouse model. Patients with advanced CKD without antithrombotic therapy show platelet preactivation with a partial secondary platelet dysfunction mainly upon collagen/GPVI stimulation. Platelets from hemodialysis patients on ASA showed a less severe CKD-associated secondary platelet dysfunction compared with those not taking ASA, with comparable observations in CKD mice on ASA vs vehicle.
{"title":"Impaired Secondary Platelet Response in Chronic Kidney Disease as a Consequence of Prior Platelet Activation","authors":"Constance C.F.M.J. Baaten PhD , Julia Wollenhaupt PhD , Tobias M. Henning MD , Sonja Vondenhoff MS , Jonas R. Schröer MD , Eleni Stamellou MD, PhD, MS , Turgay Saritas MD, PhD , Berkan Kurt MD , Leonard Boger MD , Alessandra Antwerpen , Juliane Hermann PhD , Magdolna Nagy PhD , Marieke Sternkopf PhD , Eva Miriam Buhl PhD , Ute Raffetseder PhD , Paola E.J. van der Meijden PhD , Marijke J.E. Kuijpers PhD , Henri M.H. Spronk PhD , Stefan J. Schunk MD , Joachim Jankowski PhD , Heidi Noels PhD","doi":"10.1016/j.jacbts.2025.101355","DOIUrl":"10.1016/j.jacbts.2025.101355","url":null,"abstract":"<div><div>Patients with chronic kidney disease (CKD) are at increased risk of thrombotic and hemorrhagic complications. Findings on platelet defects in CKD are conflicting. Therefore, we examined platelet function in CKD stage 3 to 5 dialysis patients without antithrombotic therapy, in CKD5D/hemodialysis patients on acetylsalicylic acid (ASA) as well as in a CKD mouse model. Patients with advanced CKD without antithrombotic therapy show platelet preactivation with a partial secondary platelet dysfunction mainly upon collagen/GPVI stimulation. Platelets from hemodialysis patients on ASA showed a less severe CKD-associated secondary platelet dysfunction compared with those not taking ASA, with comparable observations in CKD mice on ASA vs vehicle.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101355"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780540","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 : 2025-09-01Epub Date: 2025-07-29DOI: 10.1016/j.jacbts.2025.101352
W.H. Wilson Tang MD , Johannes Steiner MD , Mahwash Kassi MD , Matthew T. Wheeler MD , Aferdita Spahillari MD, MPH , Nancy K. Sweitzer MD, PhD , Justin L. Grodin MD, MPH , Neal Solomon MD , Shalabh Singhal MD , Amanda M.G. McEwen MS , Samuel L. Murphy MD
This first-in-human, phase 1, double-blind, placebo-controlled study evaluated the safety, tolerability, immunogenicity, pharmacokinetics, and exploratory efficacy of a selective ErbB4 agonist, JK07, in patients with heart failure with reduced ejection fraction (HFrEF). In these patients on optimal goal-directed medical therapy, JK07 was generally safe and well tolerated at dose levels up to 0.09 mg/kg. There was a trend toward increased incidence and severity of treatment-emergent adverse events observed at the highest dose of 0.27 mg/kg. Consistent with prolonged effects seen with transient exposure to neuregulin-1 in previous phase 1 investigations, improvements in left ventricular ejection fraction lasting up to 180 days after infusion were observed. These findings support continued clinical investigation of JK07 in heart failure. (Study of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction; NCT04210375)
{"title":"Single Ascending-Dose Study of Selective ErbB4 Agonist JK07 in Heart Failure With Reduced Ejection Fraction","authors":"W.H. Wilson Tang MD , Johannes Steiner MD , Mahwash Kassi MD , Matthew T. Wheeler MD , Aferdita Spahillari MD, MPH , Nancy K. Sweitzer MD, PhD , Justin L. Grodin MD, MPH , Neal Solomon MD , Shalabh Singhal MD , Amanda M.G. McEwen MS , Samuel L. Murphy MD","doi":"10.1016/j.jacbts.2025.101352","DOIUrl":"10.1016/j.jacbts.2025.101352","url":null,"abstract":"<div><div>This first-in-human, phase 1, double-blind, placebo-controlled study evaluated the safety, tolerability, immunogenicity, pharmacokinetics, and exploratory efficacy of a selective ErbB4 agonist, JK07, in patients with heart failure with reduced ejection fraction (HFrEF). In these patients on optimal goal-directed medical therapy, JK07 was generally safe and well tolerated at dose levels up to 0.09 mg/kg. There was a trend toward increased incidence and severity of treatment-emergent adverse events observed at the highest dose of 0.27 mg/kg. Consistent with prolonged effects seen with transient exposure to neuregulin-1 in previous phase 1 investigations, improvements in left ventricular ejection fraction lasting up to 180 days after infusion were observed. These findings support continued clinical investigation of JK07 in heart failure. (Study of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction; <span><span>NCT04210375</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101352"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722294","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 : 2025-09-01Epub Date: 2025-08-15DOI: 10.1016/j.jacbts.2025.101356
Evgeni Efimenko PhD , Hairu Zhao MS , Keith Moskowitz PhD , Conrad Smith MD , Robert Pyo MD , Thomas G. Diacovo MD
This preclinical evaluation of a prohemostatic agent involved patients who received aspirin and clopidogrel before coronary artery stenting, the use of a humanized animal model to assess the hemostatic properties of patient platelets, as well as microfluidic assays to measure platelet reactivity. We demonstrate that our investigational product can bypass the effects of dual antiplatelet therapy (DAPT) by generating thrombin at sites of vascular injury, thereby restoring the hemostatic properties of patient platelets. Importantly, its effects could be reversed upon administration of a thrombin inhibitor. Thus, this product offers a titratable and reversible strategy for the management of defective hemostasis associated with DAPT.
{"title":"Preclinical Efficacy of a Hemostatic Agent in Overcoming Dual Antiplatelet Therapy","authors":"Evgeni Efimenko PhD , Hairu Zhao MS , Keith Moskowitz PhD , Conrad Smith MD , Robert Pyo MD , Thomas G. Diacovo MD","doi":"10.1016/j.jacbts.2025.101356","DOIUrl":"10.1016/j.jacbts.2025.101356","url":null,"abstract":"<div><div>This preclinical evaluation of a prohemostatic agent involved patients who received aspirin and clopidogrel before coronary artery stenting, the use of a humanized animal model to assess the hemostatic properties of patient platelets, as well as microfluidic assays to measure platelet reactivity. We demonstrate that our investigational product can bypass the effects of dual antiplatelet therapy (DAPT) by generating thrombin at sites of vascular injury, thereby restoring the hemostatic properties of patient platelets. Importantly, its effects could be reversed upon administration of a thrombin inhibitor. Thus, this product offers a titratable and reversible strategy for the management of defective hemostasis associated with DAPT.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101356"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851915","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 : 2025-09-01Epub Date: 2025-08-15DOI: 10.1016/j.jacbts.2025.101334
Andrew A. Gibb PhD , Kyle LaPenna MD, PhD , Ryan B. Gaspar BS , Nadina R. Latchman BS , Yinfei Tan PhD , Carmen Choya-Foces PhD , Jake E. Doiron PhD , Zhen Li PhD , Huijing Xia PhD , Michael P. Lazaropoulos PhD , Mariell Conwell BS , Thomas E. Sharp III PhD , Traci T. Goodchild PhD , David J. Lefer PhD , John W. Elrod PhD
Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of HF cases. The ZSF1-obese rat model recapitulates clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and diastolic dysfunction. We utilized a systems-biology approach to define the metabolic and transcriptional signatures to gain mechanistic insight into pathways contributing to HFpEF development. Male ZSF1-obese, ZSF1-lean hypertensive controls, and WKY (wild-type) controls were compared at 14 weeks of age for extensive physiological phenotyping and left ventricle (LV) tissue harvesting for unbiased-metabolomics, RNA-sequencing, and mitochondrial morphology and function. Utilizing ZSF1-lean and WKY controls enabled a distinction between hypertension-driven molecular changes driving HFpEF pathology, versus hypertension + metabolic syndrome. Comparison of ZSF1-lean vs WKY (ie, hypertension-exclusive effects) revealed metabolic remodeling suggesting increased aerobic glycolysis, decreased β-oxidation, and dysregulated purine and pyrimidine metabolism with few transcriptional changes. ZSF1-obese rats displayed worsened metabolic remodeling and robust transcriptional remodeling highlighted by upregulation of inflammatory genes and downregulation of the mitochondrial structure/function and metabolic processes. Integrated network analysis of metabolomic and RNAseq datasets revealed downregulation of most catabolic energy producing pathways, manifesting in a marked decrease in the energetic state (ie, reduced ATP/ADP, PCr/ATP). Cardiomyocyte ultrastructure analysis revealed decreased mitochondrial area, size, and cristae density, as well as increased lipid droplet content in HFpEF hearts. Impaired mitochondrial function was demonstrated by decreased substrate-mediated respiration and dysregulated calcium handling. Collectively, the integrated omics approach applied here provides a framework to uncover novel genes, metabolites, and pathways underlying HFpEF, with an emphasis on mitochondrial energy metabolism as a potential interventional target.
{"title":"Integrated Systems Biology Identifies Disruptions in Mitochondrial Function and Metabolism as Key Contributors to HFpEF","authors":"Andrew A. Gibb PhD , Kyle LaPenna MD, PhD , Ryan B. Gaspar BS , Nadina R. Latchman BS , Yinfei Tan PhD , Carmen Choya-Foces PhD , Jake E. Doiron PhD , Zhen Li PhD , Huijing Xia PhD , Michael P. Lazaropoulos PhD , Mariell Conwell BS , Thomas E. Sharp III PhD , Traci T. Goodchild PhD , David J. Lefer PhD , John W. Elrod PhD","doi":"10.1016/j.jacbts.2025.101334","DOIUrl":"10.1016/j.jacbts.2025.101334","url":null,"abstract":"<div><div>Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of HF cases. The ZSF1-obese rat model recapitulates clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and diastolic dysfunction. We utilized a systems-biology approach to define the metabolic and transcriptional signatures to gain mechanistic insight into pathways contributing to HFpEF development. Male ZSF1-obese, ZSF1-lean hypertensive controls, and WKY (wild-type) controls were compared at 14 weeks of age for extensive physiological phenotyping and left ventricle (LV) tissue harvesting for unbiased-metabolomics, RNA-sequencing, and mitochondrial morphology and function. Utilizing ZSF1-lean and WKY controls enabled a distinction between hypertension-driven molecular changes driving HFpEF pathology, versus hypertension + metabolic syndrome. Comparison of ZSF1-lean vs WKY (ie, hypertension-exclusive effects) revealed metabolic remodeling suggesting increased aerobic glycolysis, decreased β-oxidation, and dysregulated purine and pyrimidine metabolism with few transcriptional changes. ZSF1-obese rats displayed worsened metabolic remodeling and robust transcriptional remodeling highlighted by upregulation of inflammatory genes and downregulation of the mitochondrial structure/function and metabolic processes. Integrated network analysis of metabolomic and RNAseq datasets revealed downregulation of most catabolic energy producing pathways, manifesting in a marked decrease in the energetic state (ie, reduced ATP/ADP, PCr/ATP). Cardiomyocyte ultrastructure analysis revealed decreased mitochondrial area, size, and cristae density, as well as increased lipid droplet content in HFpEF hearts. Impaired mitochondrial function was demonstrated by decreased substrate-mediated respiration and dysregulated calcium handling. Collectively, the integrated omics approach applied here provides a framework to uncover novel genes, metabolites, and pathways underlying HFpEF, with an emphasis on mitochondrial energy metabolism as a potential interventional target.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101334"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851797","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 : 2025-09-01Epub Date: 2025-08-11DOI: 10.1016/j.jacbts.2025.101357
Chae-Myeong Ha PhD, Adam R. Wende PhD
{"title":"Cracking the Code of a Preclinical Rodent Model of HFpEF","authors":"Chae-Myeong Ha PhD, Adam R. Wende PhD","doi":"10.1016/j.jacbts.2025.101357","DOIUrl":"10.1016/j.jacbts.2025.101357","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101357"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809871","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 : 2025-09-01Epub Date: 2025-08-20DOI: 10.1016/j.jacbts.2025.101327
Avinash B. Khandagale PhD , Padraic Corcoran PhD , Yuzhen Dan PhD , Anders Isaksson PhD , Stefan James MD, PhD , Agneta Siegbahn MD, PhD , Christina Christersson MD, PhD
Extracellular vesicles (EVs) and microRNAs (miRs) have been found to be differently expressed in patients with aortic valve stenosis (AS). Here, we profiled the expression of miRs associated with circulating EVs from severe AS patients and found several altered miRs compared with healthy counterparts. EVs from AS patients induced calcification through expression of the pro-osteogenic genes osteocalcin and osteopontin with corresponding proteins. The expression levels of miR-455-3p and miR-103a-3p were found correlated to the calcification of VICs. Alteration in these miR abrogated osteogenic differentiation of VICs. Additionally, BMP4 and transcriptional factor RUNX2 were found affected by these miRs.
{"title":"Plasma-Derived Extracellular Vesicle-Propagated microRNA From Aortic Stenosis Patients Render Pro-Calcifying Effects on Valve Interstitial Cells","authors":"Avinash B. Khandagale PhD , Padraic Corcoran PhD , Yuzhen Dan PhD , Anders Isaksson PhD , Stefan James MD, PhD , Agneta Siegbahn MD, PhD , Christina Christersson MD, PhD","doi":"10.1016/j.jacbts.2025.101327","DOIUrl":"10.1016/j.jacbts.2025.101327","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) and microRNAs (miRs) have been found to be differently expressed in patients with aortic valve stenosis (AS). Here, we profiled the expression of miRs associated with circulating EVs from severe AS patients and found several altered miRs compared with healthy counterparts. EVs from AS patients induced calcification through expression of the pro-osteogenic genes osteocalcin and osteopontin with corresponding proteins. The expression levels of miR-455-3p and miR-103a-3p were found correlated to the calcification of VICs. Alteration in these miR abrogated osteogenic differentiation of VICs. Additionally, BMP4 and transcriptional factor RUNX2 were found affected by these miRs.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101327"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863905","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 : 2025-09-01Epub Date: 2025-08-20DOI: 10.1016/j.jacbts.2025.101371
Senthil Selvaraj MD, MS, MA , G. Michael Felker MD, MHS
{"title":"Therapeutic Implications of ErbB Pathway Modification in Heart Failure with Reduced Ejection Fraction","authors":"Senthil Selvaraj MD, MS, MA , G. Michael Felker MD, MHS","doi":"10.1016/j.jacbts.2025.101371","DOIUrl":"10.1016/j.jacbts.2025.101371","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101371"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879347","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 : 2025-09-01Epub Date: 2025-07-30DOI: 10.1016/j.jacbts.2025.03.014
Daniel Diaz-Gil MD , Gregor Gierlinger MD , Natalia Silva-Gomez Cand Med , Lavinia Rech MD, PhD , Jesus Ortiz-Urbina MD , Kerstin Saraci Cand Med , Sophia Koutsogiannaki PhD , Cordula M. Wolf MD , Rainer G. Kozlik-Feldmann MD , Rudolf Mair MD , Juan M. Melero-Martin PhD , Sitaram M. Emani MD , Guillermo García-Cardeña PhD , Pedro J. del Nido MD , Ingeborg Friehs MD
Endocardial fibroelastosis is a condition caused by the fibrogenic activation of endothelial cells via endothelial-to-mesenchymal transition of the endocardium, which is regulated by the transforming growth factor-β pathway. Atorvastatin, a statin, can protect the vascular endothelium by up-regulating KLF2 and inhibiting the transforming growth factor-β pathway. This study aimed to investigate the effects of atorvastatin on the fibrogenic activation of endothelial cells in the endocardium. The study found that atorvastatin treatment reduced fibrogenic activation of endocardial endothelial cells and increased KLF2 expression in both in vitro and in vivo models of endocardial fibroelastosis–related left ventricular restriction.
{"title":"Preclinical Assessment of Atorvastatin for Treatment of Endocardial Fibroelastosis","authors":"Daniel Diaz-Gil MD , Gregor Gierlinger MD , Natalia Silva-Gomez Cand Med , Lavinia Rech MD, PhD , Jesus Ortiz-Urbina MD , Kerstin Saraci Cand Med , Sophia Koutsogiannaki PhD , Cordula M. Wolf MD , Rainer G. Kozlik-Feldmann MD , Rudolf Mair MD , Juan M. Melero-Martin PhD , Sitaram M. Emani MD , Guillermo García-Cardeña PhD , Pedro J. del Nido MD , Ingeborg Friehs MD","doi":"10.1016/j.jacbts.2025.03.014","DOIUrl":"10.1016/j.jacbts.2025.03.014","url":null,"abstract":"<div><div>Endocardial fibroelastosis is a condition caused by the fibrogenic activation of endothelial cells via endothelial-to-mesenchymal transition of the endocardium, which is regulated by the transforming growth factor-β pathway. Atorvastatin, a statin, can protect the vascular endothelium by up-regulating KLF2 and inhibiting the transforming growth factor-β pathway. This study aimed to investigate the effects of atorvastatin on the fibrogenic activation of endothelial cells in the endocardium. The study found that atorvastatin treatment reduced fibrogenic activation of endocardial endothelial cells and increased KLF2 expression in both in vitro and in vivo models of endocardial fibroelastosis–related left ventricular restriction.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101282"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753422","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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