Pub Date : 2025-12-16DOI: 10.1161/cir.0000000000001390
Andrew H Tran,Abbas H Zaidi,Ann F Bolger,Oscar H Del Brutto,Rashmi Hegde,Lauren L Patton,Jamie Rausch,Justin P Zachariah,
Since the publication of the 2012 American Heart Association scientific statement on the association between periodontal disease and atherosclerotic cardiovascular disease, the body of literature on this topic has grown substantially. Atherosclerotic cardiovascular disease is the leading cause of death globally, and understanding contributors and potential targets to decrease this risk is paramount. This updated scientific statement synthesizes new evidence concerning an association between periodontal disease and atherosclerotic cardiovascular disease, including findings from Mendelian randomization studies, interventions targeting periodontal disease, and studies exploring systemic markers, such as inflammatory cytokines and vascular measures. The scientific statement also highlights disparities in the prevalence of periodontal disease, particularly among underresourced populations; explores potential mechanisms linking periodontal disease with cardiovascular outcomes through direct pathways, such as bacteremia, and indirect pathways, such as chronic systemic inflammation; and identifies areas needing further clarification that would benefit from additional research.
{"title":"Periodontal Disease and Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association.","authors":"Andrew H Tran,Abbas H Zaidi,Ann F Bolger,Oscar H Del Brutto,Rashmi Hegde,Lauren L Patton,Jamie Rausch,Justin P Zachariah, ","doi":"10.1161/cir.0000000000001390","DOIUrl":"https://doi.org/10.1161/cir.0000000000001390","url":null,"abstract":"Since the publication of the 2012 American Heart Association scientific statement on the association between periodontal disease and atherosclerotic cardiovascular disease, the body of literature on this topic has grown substantially. Atherosclerotic cardiovascular disease is the leading cause of death globally, and understanding contributors and potential targets to decrease this risk is paramount. This updated scientific statement synthesizes new evidence concerning an association between periodontal disease and atherosclerotic cardiovascular disease, including findings from Mendelian randomization studies, interventions targeting periodontal disease, and studies exploring systemic markers, such as inflammatory cytokines and vascular measures. The scientific statement also highlights disparities in the prevalence of periodontal disease, particularly among underresourced populations; explores potential mechanisms linking periodontal disease with cardiovascular outcomes through direct pathways, such as bacteremia, and indirect pathways, such as chronic systemic inflammation; and identifies areas needing further clarification that would benefit from additional research.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"68 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759935","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 : 2025-12-16Epub Date: 2025-11-24DOI: 10.1161/CIRCULATIONAHA.125.075057
Julian S Wanner, Maren Krafft, Teemu Niiranen, Dominic S Zimmerman, FinnGen, Patrick T Ellinor, Girish Nadkarni, Sean J Jurgens, Joel Rämö, Henrike O Heyne
Background: Atrial fibrillation and other cardiac arrhythmias pose a major public health burden, but prevention remains difficult. We investigated a genetic variant that we found to act like a natural lifelong cardiac sodium channel blockade.
Methods: We studied the impact of the Finnish-enriched SCN5A missense variant (rs45620037 [T220I]) on cardiac arrhythmias, associated mortality, and ECG phenotypes in a multicohort observational study with >1 million individuals across 3 cohorts (FinnGen, UK Biobank, and Health 2000).
Results: We identified protective effects of T220I on multiple common cardiac arrhythmias, most notably atrial fibrillation (cause-specific hazard ratio [HR], 0.56 [95% CI, 0.50-0.63]; P<0.0001), but also ventricular premature depolarization or ventricular tachycardia, as well as increasing susceptibility to conduction-slowing conditions, such as sick sinus syndrome (mostly in older age groups). Overall, T220I conveyed protection from death resulting from cardiac arrhythmia (HR, 0.65 [95% CI, 0.46-0.92]; P=0.015) without a significant effect on overall mortality risk (HR, 0.92; P=0.27). T220I heterozygosity had similar electrophysiological effects as some pharmacological sodium channel blockers, such as significantly shortening QT intervals (-7.49 ms [95% CI, -10.07 to -4.91] ms; P=0.0037; n=3188) in the Health 2000 cohort, which we replicated in the UK Biobank (n=66 616). In addition, T220I protected from (left) heart failure and dilated cardiomyopathy. After myocardial infarction, we found that T220I increased mortality risk, consistent with known sodium channel blocker effects, which, however, normalized to baseline 10 to 15 years after myocardial infarction. We found that T220I could lower a high genetic burden (ie, a high polygenic score) for atrial fibrillation to population average.
Conclusions: The SCN5A T220I variant, consistent with a previously described weak loss-of-function effect, acted like a genetic proxy for cardiac sodium channel blockade. This enabled us to gain new potentially clinically relevant insights for pharmacological sodium channel blockade, such as after myocardial infarction, which would be too risky to investigate with clinical trials. Our findings may also inspire redesign of cardiac sodium channel blockers.
{"title":"Leveraging a Genetic Proxy to Investigate the Effects of Lifelong Cardiac Sodium Channel Blockade.","authors":"Julian S Wanner, Maren Krafft, Teemu Niiranen, Dominic S Zimmerman, FinnGen, Patrick T Ellinor, Girish Nadkarni, Sean J Jurgens, Joel Rämö, Henrike O Heyne","doi":"10.1161/CIRCULATIONAHA.125.075057","DOIUrl":"10.1161/CIRCULATIONAHA.125.075057","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation and other cardiac arrhythmias pose a major public health burden, but prevention remains difficult. We investigated a genetic variant that we found to act like a natural lifelong cardiac sodium channel blockade.</p><p><strong>Methods: </strong>We studied the impact of the Finnish-enriched <i>SCN5A</i> missense variant (rs45620037 [T220I]) on cardiac arrhythmias, associated mortality, and ECG phenotypes in a multicohort observational study with >1 million individuals across 3 cohorts (FinnGen, UK Biobank, and Health 2000).</p><p><strong>Results: </strong>We identified protective effects of T220I on multiple common cardiac arrhythmias, most notably atrial fibrillation (cause-specific hazard ratio [HR], 0.56 [95% CI, 0.50-0.63]; <i>P</i><0.0001), but also ventricular premature depolarization or ventricular tachycardia, as well as increasing susceptibility to conduction-slowing conditions, such as sick sinus syndrome (mostly in older age groups). Overall, T220I conveyed protection from death resulting from cardiac arrhythmia (HR, 0.65 [95% CI, 0.46-0.92]; <i>P</i>=0.015) without a significant effect on overall mortality risk (HR, 0.92; <i>P</i>=0.27). T220I heterozygosity had similar electrophysiological effects as some pharmacological sodium channel blockers, such as significantly shortening QT intervals (-7.49 ms [95% CI, -10.07 to -4.91] ms; <i>P</i>=0.0037; n=3188) in the Health 2000 cohort, which we replicated in the UK Biobank (n=66 616). In addition, T220I protected from (left) heart failure and dilated cardiomyopathy. After myocardial infarction, we found that T220I increased mortality risk, consistent with known sodium channel blocker effects, which, however, normalized to baseline 10 to 15 years after myocardial infarction. We found that T220I could lower a high genetic burden (ie, a high polygenic score) for atrial fibrillation to population average.</p><p><strong>Conclusions: </strong>The <i>SCN5A</i> T220I variant, consistent with a previously described weak loss-of-function effect, acted like a genetic proxy for cardiac sodium channel blockade. This enabled us to gain new potentially clinically relevant insights for pharmacological sodium channel blockade, such as after myocardial infarction, which would be too risky to investigate with clinical trials. Our findings may also inspire redesign of cardiac sodium channel blockers.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1679-1690"},"PeriodicalIF":38.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12700700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586205","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}
Pub Date : 2025-12-15DOI: 10.1161/circulationaha.125.078028
Xinpei Wang,Huijian Liu,Qing Lu
{"title":"A Storm of Tachycardia Following Stroke: What Is the Mechanism?","authors":"Xinpei Wang,Huijian Liu,Qing Lu","doi":"10.1161/circulationaha.125.078028","DOIUrl":"https://doi.org/10.1161/circulationaha.125.078028","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"21 1","pages":"1732-1734"},"PeriodicalIF":37.8,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759937","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 : 2025-12-15DOI: 10.1161/circulationaha.125.076838
Signe Glargaard,Jens Jakob Thune
{"title":"Response by Glargaard and Thune to Letters Regarding Article, \"A Randomized Trial of Thoracentesis in Acute Heart Failure\".","authors":"Signe Glargaard,Jens Jakob Thune","doi":"10.1161/circulationaha.125.076838","DOIUrl":"https://doi.org/10.1161/circulationaha.125.076838","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"246 1","pages":"e472-e473"},"PeriodicalIF":37.8,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759940","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 : 2025-12-15DOI: 10.1161/circulationaha.125.075311
Andrea Boccatonda,Damiano D'Ardes,Francesco Cipollone
{"title":"Letter by Boccatonda et al Regarding Article, \"A Randomized Controlled Trial of Thoracentesis in Acute Heart Failure\".","authors":"Andrea Boccatonda,Damiano D'Ardes,Francesco Cipollone","doi":"10.1161/circulationaha.125.075311","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075311","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"77 1","pages":"e469-e470"},"PeriodicalIF":37.8,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759942","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 : 2025-12-15DOI: 10.1161/circulationaha.125.075122
Jiawei Lei,Fei Zhang,Jiahe Wang
{"title":"Letter by Lei et al Regarding Article, \"A Randomized Controlled Trial of Thoracentesis in Acute Heart Failure\".","authors":"Jiawei Lei,Fei Zhang,Jiahe Wang","doi":"10.1161/circulationaha.125.075122","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075122","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"21 1","pages":"e467-e468"},"PeriodicalIF":37.8,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760001","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 : 2025-12-15DOI: 10.1161/circulationaha.125.077743
Daniel Bernstein,Giovanni Fajardo
{"title":"Hypertrophic Cardiomyopathy is a Disease of Altered Metabolism: Interdependence of Hypercontractility, Oxidative Stress, and Creatine Kinase Dysfunction.","authors":"Daniel Bernstein,Giovanni Fajardo","doi":"10.1161/circulationaha.125.077743","DOIUrl":"https://doi.org/10.1161/circulationaha.125.077743","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"11 1","pages":"1728-1731"},"PeriodicalIF":37.8,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759936","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 : 2025-12-11DOI: 10.1161/circulationaha.124.071351
Fang Li,Bibek Poudel,Magaiver Andrade-Silva,Junnan Wu,Archana Raman,Elisa Cruz-Morales,Joseph Wahba,Allison Vassalotti,Chenyu Li,Amin Abedini,Konstantin A Klötzer,Xiaoqiang Ding,Christopher A Hunter,Jonathan J Miner,Katalin Susztak
BACKGROUNDBlack people bear a disproportionate burden of hypertension and hypertension-attributed chronic kidney disease. A role of apolipoprotein L1 (APOL1) risk variants (RVs; G1 and G2) in these conditions has been proposed, but genetic and observational studies have shown inconsistent results.METHODSHere, we investigated the causal role of APOL1 RVs using patient samples, transgenic animal models, and in vitro primary cellular experiments.RESULTSIn the human kidney, APOL1 was highly expressed by glomerular podocytes and endothelial cells. Mice with podocyte-specific expression of the APOL1 RV (G2APOL1), but not those with the reference allele (G0), developed severe secondary hypertension after albuminuria and kidney disease. Mice expressing endothelium-specific G2APOL1 RVs developed mild hypertension with aging, which was exacerbated after unilateral nephrectomy and subsequent high-salt diet feeding. This condition was associated with a slight alteration in kidney function. In vitro and in vivo experiments demonstrated that the APOL1 RV activates the cytosolic nucleotide sensor STING (stimulator of interferon genes), leading to increased production of endothelin 1. Notably, mice with endothelium-specific STING knockout or those treated with an endothelin inhibitor showed protection from G2APOL1 RV-mediated hypertension.CONCLUSIONSThese findings indicate a role of G2APOL1 in hypertension development through STING and endothelin 1 activation, offering new precision therapeutics for addressing hypertension in Black people carrying APOL1 RVs.
{"title":"Cell-Specific Inducible Human APOL1 Risk Variant Expression in Mice Causes Hypertension and Renal Damage.","authors":"Fang Li,Bibek Poudel,Magaiver Andrade-Silva,Junnan Wu,Archana Raman,Elisa Cruz-Morales,Joseph Wahba,Allison Vassalotti,Chenyu Li,Amin Abedini,Konstantin A Klötzer,Xiaoqiang Ding,Christopher A Hunter,Jonathan J Miner,Katalin Susztak","doi":"10.1161/circulationaha.124.071351","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071351","url":null,"abstract":"BACKGROUNDBlack people bear a disproportionate burden of hypertension and hypertension-attributed chronic kidney disease. A role of apolipoprotein L1 (APOL1) risk variants (RVs; G1 and G2) in these conditions has been proposed, but genetic and observational studies have shown inconsistent results.METHODSHere, we investigated the causal role of APOL1 RVs using patient samples, transgenic animal models, and in vitro primary cellular experiments.RESULTSIn the human kidney, APOL1 was highly expressed by glomerular podocytes and endothelial cells. Mice with podocyte-specific expression of the APOL1 RV (G2APOL1), but not those with the reference allele (G0), developed severe secondary hypertension after albuminuria and kidney disease. Mice expressing endothelium-specific G2APOL1 RVs developed mild hypertension with aging, which was exacerbated after unilateral nephrectomy and subsequent high-salt diet feeding. This condition was associated with a slight alteration in kidney function. In vitro and in vivo experiments demonstrated that the APOL1 RV activates the cytosolic nucleotide sensor STING (stimulator of interferon genes), leading to increased production of endothelin 1. Notably, mice with endothelium-specific STING knockout or those treated with an endothelin inhibitor showed protection from G2APOL1 RV-mediated hypertension.CONCLUSIONSThese findings indicate a role of G2APOL1 in hypertension development through STING and endothelin 1 activation, offering new precision therapeutics for addressing hypertension in Black people carrying APOL1 RVs.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"1 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718014","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}
BACKGROUNDCardiac fibrosis is a major determinant of adverse clinical outcomes of many heart diseases; currently, therapeutic strategy directly targeting fibroblasts is lacking. Nitric oxide-mediated nitrosative stress is associated with cardiac injury, and excessive nitric oxide can trigger S-nitrosylation (SNO) to specific cysteine thiol. This study aims to investigate the role of SNO in cardiac fibrosis and to identify potential therapeutic target.METHODSSNO proteomic analysis was performed in cardiac tissue isolated from both mice subjected to transverse aortic constriction and spontaneous hypertensive rats. Elevated SNO of pyruvate kinase M2 (PKM2) was identified in cardiac fibroblasts, which was merely detected in cardiomyocytes. Cardiac fibroblast-specific PKM2 knockout mice and mice transfected with wild-type or SNO-resistant PKM2 mutant were used to determine the involvement of SNO of PKM2 (SNO-PKM2) in cardiac fibrosis. Unbiased proteomics and coimmunoprecipitation combined with mass spectrometry analysis were conducted to explore effectors mediating SNO-PKM2-induced activation of cardiac fibroblasts. A recently approved drug for rare blood disorder, mitapivat, was shown to dose-dependently relieve cardiac fibrosis.RESULTSSNO of PKM2 at cysteine 49 and 326 increased in the heart tissue of patients with heart failure, heart tissue of murine cardiac fibrosis models, and cardiac fibroblasts stimulated with angiotensin II. SNO-PKM2 reduced pyruvate kinase activity and tetramerization of PKM2, and cardiac fibroblast-specific PKM2 knockout aggravated cardiac fibrosis, whereas cardiac fibroblast-specific PKM2 knockout mice transfected with SNO-resistant mutant rather than wild-type PKM2 had cardiac function. Mechanistically, SNO-PKM2 drove excessive mitochondrial fission and mitochondrial dysfunction through interfering with its interaction with actin regulatory protein gelsolin. TEPP-46, a pharmacological PKM2 activator, alleviated mitochondrial fission and cardiac fibrosis. Moreover, the US Food and Drug Administration-approved drug mitapivat showed preventive and therapeutical effects on cardiac fibrosis through activating PKM2.CONCLUSIONSSNO-PKM2 specifically increases in cardiac fibroblasts and activated cardiac fibroblasts by inducing excessive mitochondrial fission through a gelsolin-dependent manner. Mitapivat is a potential therapeutic option for attenuating cardiac fibrosis.
{"title":"S-Nitrosylation of Pyruvate Kinase Isoform 2 Drives Cardiac Fibrosis by Promoting Mitochondrial Fission.","authors":"Shanshan Luo,Danyu Ye,Yan Zhang,Yu Wang,Miao Zhou,Mengqi Lv,Xiaoqian Wang,Ke Zhong,Yuxiao Zhang,Lulu Hu,Shixiu Sun,Zhiren Zhang,Bo Yu,Changhao Sun,Xiangqing Kong,Zhengrong Huang,Xin Chen,Yi Han,Liping Xie,Yong Ji","doi":"10.1161/circulationaha.125.075903","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075903","url":null,"abstract":"BACKGROUNDCardiac fibrosis is a major determinant of adverse clinical outcomes of many heart diseases; currently, therapeutic strategy directly targeting fibroblasts is lacking. Nitric oxide-mediated nitrosative stress is associated with cardiac injury, and excessive nitric oxide can trigger S-nitrosylation (SNO) to specific cysteine thiol. This study aims to investigate the role of SNO in cardiac fibrosis and to identify potential therapeutic target.METHODSSNO proteomic analysis was performed in cardiac tissue isolated from both mice subjected to transverse aortic constriction and spontaneous hypertensive rats. Elevated SNO of pyruvate kinase M2 (PKM2) was identified in cardiac fibroblasts, which was merely detected in cardiomyocytes. Cardiac fibroblast-specific PKM2 knockout mice and mice transfected with wild-type or SNO-resistant PKM2 mutant were used to determine the involvement of SNO of PKM2 (SNO-PKM2) in cardiac fibrosis. Unbiased proteomics and coimmunoprecipitation combined with mass spectrometry analysis were conducted to explore effectors mediating SNO-PKM2-induced activation of cardiac fibroblasts. A recently approved drug for rare blood disorder, mitapivat, was shown to dose-dependently relieve cardiac fibrosis.RESULTSSNO of PKM2 at cysteine 49 and 326 increased in the heart tissue of patients with heart failure, heart tissue of murine cardiac fibrosis models, and cardiac fibroblasts stimulated with angiotensin II. SNO-PKM2 reduced pyruvate kinase activity and tetramerization of PKM2, and cardiac fibroblast-specific PKM2 knockout aggravated cardiac fibrosis, whereas cardiac fibroblast-specific PKM2 knockout mice transfected with SNO-resistant mutant rather than wild-type PKM2 had cardiac function. Mechanistically, SNO-PKM2 drove excessive mitochondrial fission and mitochondrial dysfunction through interfering with its interaction with actin regulatory protein gelsolin. TEPP-46, a pharmacological PKM2 activator, alleviated mitochondrial fission and cardiac fibrosis. Moreover, the US Food and Drug Administration-approved drug mitapivat showed preventive and therapeutical effects on cardiac fibrosis through activating PKM2.CONCLUSIONSSNO-PKM2 specifically increases in cardiac fibroblasts and activated cardiac fibroblasts by inducing excessive mitochondrial fission through a gelsolin-dependent manner. Mitapivat is a potential therapeutic option for attenuating cardiac fibrosis.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"1 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710830","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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