{"title":"Telomer length, integrity vs. telomerase-activity - who is to blame for heart failure?","authors":"Petra Kleinbongard, Andreas M Beyer","doi":"10.1093/cvr/cvag026","DOIUrl":"https://doi.org/10.1093/cvr/cvag026","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112209","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}
Philipp Hegner, Maria J Baier, Thomas Krammer, Simon Seitz, Anna-Katharina Käs, Tilman Zschiedrich, David Lukas, Vanessa Lutz, Matthias Wolf, Frederick Sinha, Simon Schopka, Christof Schmid, Kostiantyn Kozakov, Zdenek Provaznik, Lars S Maier, Julian Mustroph, Stefan Wagner
{"title":"Semaglutide improves contractile function in human atrial myocardium of patients with heart failure and preserved ejection fraction.","authors":"Philipp Hegner, Maria J Baier, Thomas Krammer, Simon Seitz, Anna-Katharina Käs, Tilman Zschiedrich, David Lukas, Vanessa Lutz, Matthias Wolf, Frederick Sinha, Simon Schopka, Christof Schmid, Kostiantyn Kozakov, Zdenek Provaznik, Lars S Maier, Julian Mustroph, Stefan Wagner","doi":"10.1093/cvr/cvag039","DOIUrl":"https://doi.org/10.1093/cvr/cvag039","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112219","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}
Konstantinos I Karampinos,Dimitrios Farmakis,Rijan Gurung,Roger S-Y Foo,Gerasimos S Filippatos,Dennis V Cokkinos
Ferroptosis is the form of regulated cell death driven by iron-induced lipid peroxidation, implicated in different cardiovascular diseases and especially heart failure. It is an abundant form of regulated cell death in the myocardium of many heart failure animal models, including the chronic ischemic, pressure overload, diabetic, septic, obesity-related and doxorubicin-induced cardiomyopathy models. Across these models, disordered iron handling, antioxidant failure, enzymatic phospholipid peroxidation, and mitochondrial stress converge on ferroptosis, leading to contractile dysfunction and adverse remodelling. Although definitive causality between ferroptosis and heart failure has not yet been established, emerging evidence suggests that ferroptosis contributes to heart failure progression, supported by multi-layer rescue with classic inhibitors (ferrostatin-1, liproxstatin-1, iron chelators) and by cardiometabolic drugs with clinical efficacy in heart failure (Sodium-Glucose Cotransporter 2 inhibitors, sacubitril/valsartan, finerenone, levosimendan, nicorandil) as well as polyphenols, which restore systolic and/or diastolic indices and reverse remodelling. Early human evidence aligns, showing that human failing myocardial and epicardial adipose tissue exhibit ferroptosis-specific transcriptional and lipidomic signatures, while circulating biomarkers and tissue profiles of patients receiving SGLT2 inhibitors indicate reduced ferroptosis activity. In this review, through critical synthesis of existing evidence, we analyse current literature, discuss translational barriers and propose a new conceptual mechanistic framework - "the ferroptosis nexus" - wherein iron mobilization, antioxidant collapse, lipid priming, and mitochondrial/calcium amplifiers form a self-reinforcing loop culminating in pump failure. Standardized ferroptosis signatures, single cell and spatial transcriptomics analysis, and mechanism-driven clinical trials are needed to identify responsive heart failure phenotypes and translate ferroptosis modulation into precision cardioprotection.
{"title":"Ferroptosis in heart failure: from molecular insights to therapeutic implications.","authors":"Konstantinos I Karampinos,Dimitrios Farmakis,Rijan Gurung,Roger S-Y Foo,Gerasimos S Filippatos,Dennis V Cokkinos","doi":"10.1093/cvr/cvag019","DOIUrl":"https://doi.org/10.1093/cvr/cvag019","url":null,"abstract":"Ferroptosis is the form of regulated cell death driven by iron-induced lipid peroxidation, implicated in different cardiovascular diseases and especially heart failure. It is an abundant form of regulated cell death in the myocardium of many heart failure animal models, including the chronic ischemic, pressure overload, diabetic, septic, obesity-related and doxorubicin-induced cardiomyopathy models. Across these models, disordered iron handling, antioxidant failure, enzymatic phospholipid peroxidation, and mitochondrial stress converge on ferroptosis, leading to contractile dysfunction and adverse remodelling. Although definitive causality between ferroptosis and heart failure has not yet been established, emerging evidence suggests that ferroptosis contributes to heart failure progression, supported by multi-layer rescue with classic inhibitors (ferrostatin-1, liproxstatin-1, iron chelators) and by cardiometabolic drugs with clinical efficacy in heart failure (Sodium-Glucose Cotransporter 2 inhibitors, sacubitril/valsartan, finerenone, levosimendan, nicorandil) as well as polyphenols, which restore systolic and/or diastolic indices and reverse remodelling. Early human evidence aligns, showing that human failing myocardial and epicardial adipose tissue exhibit ferroptosis-specific transcriptional and lipidomic signatures, while circulating biomarkers and tissue profiles of patients receiving SGLT2 inhibitors indicate reduced ferroptosis activity. In this review, through critical synthesis of existing evidence, we analyse current literature, discuss translational barriers and propose a new conceptual mechanistic framework - \"the ferroptosis nexus\" - wherein iron mobilization, antioxidant collapse, lipid priming, and mitochondrial/calcium amplifiers form a self-reinforcing loop culminating in pump failure. Standardized ferroptosis signatures, single cell and spatial transcriptomics analysis, and mechanism-driven clinical trials are needed to identify responsive heart failure phenotypes and translate ferroptosis modulation into precision cardioprotection.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"8 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089066","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}
AIMSCCAAT-enhancer-binding protein (C/EBP) β is a member of the basic leucine zipper transcription factor family that regulates cell differentiation, proliferation, cell death and survival, and inflammation. Although C/EBPβ plays both protective and detrimental roles in the heart at baseline and during stress, the cell type-specific functions of C/EBPβ in the heart are unknown. Here, we investigated the role of endogenous C/EBPβ in cardiomyocytes during pressure overload-induced heart failure.METHODS AND RESULTSWe found that C/EBPβ expression was reduced in wild-type (WT) mouse heart homogenates after 4 weeks of transverse aortic constriction (TAC). To elucidate the role of endogenous C/EBPβ during cardiac stress in vivo, we generated cardiomyocyte-specific Cebpb knockout (Cebpb-cKO) mice. Cebpb-cKO mice were born at a normal Mendelian ratio but displayed slightly decreased cardiac function under baseline conditions, starting at 3 months of age. Notably, in contrast to a previous report using systemic heterozygous Cebpb-knockout mice, which exhibited cardiac protection against TAC, Cebpb-cKO mice showed significantly exacerbated systolic dysfunction, cardiac hypertrophy, and fibrosis after 4 weeks of TAC. Cebpb-cKO mice also exhibited decreased expression of antioxidant genes, including Mnsod and Catalase, both at baseline and under TAC conditions. On the other hand, rescue of the C/EBPβ level in cardiomyocytes using AAV9-cTnT-Cebpb alleviated the left ventricular (LV) dysfunction in response to TAC.CONCLUSIONSOur findings suggest that C/EBPβ has a cell-type specific role in the heart and that endogenous C/EBPβ in cardiomyocytes plays a salutary role during pressure overload.
{"title":"Cardiomyocyte-specific deficiency of C/EBPβ aggravates pressure overload-induced heart failure.","authors":"Jihoon Nah,Eun-Ah Sung,Peiyong Zhai,Yasuhiro Maejima,Chengchen Hu,Jacqueline Ramos-Zepeda,Shohei Ikeda,Wataru Mizushima,Junichi Sadoshima","doi":"10.1093/cvr/cvag029","DOIUrl":"https://doi.org/10.1093/cvr/cvag029","url":null,"abstract":"AIMSCCAAT-enhancer-binding protein (C/EBP) β is a member of the basic leucine zipper transcription factor family that regulates cell differentiation, proliferation, cell death and survival, and inflammation. Although C/EBPβ plays both protective and detrimental roles in the heart at baseline and during stress, the cell type-specific functions of C/EBPβ in the heart are unknown. Here, we investigated the role of endogenous C/EBPβ in cardiomyocytes during pressure overload-induced heart failure.METHODS AND RESULTSWe found that C/EBPβ expression was reduced in wild-type (WT) mouse heart homogenates after 4 weeks of transverse aortic constriction (TAC). To elucidate the role of endogenous C/EBPβ during cardiac stress in vivo, we generated cardiomyocyte-specific Cebpb knockout (Cebpb-cKO) mice. Cebpb-cKO mice were born at a normal Mendelian ratio but displayed slightly decreased cardiac function under baseline conditions, starting at 3 months of age. Notably, in contrast to a previous report using systemic heterozygous Cebpb-knockout mice, which exhibited cardiac protection against TAC, Cebpb-cKO mice showed significantly exacerbated systolic dysfunction, cardiac hypertrophy, and fibrosis after 4 weeks of TAC. Cebpb-cKO mice also exhibited decreased expression of antioxidant genes, including Mnsod and Catalase, both at baseline and under TAC conditions. On the other hand, rescue of the C/EBPβ level in cardiomyocytes using AAV9-cTnT-Cebpb alleviated the left ventricular (LV) dysfunction in response to TAC.CONCLUSIONSOur findings suggest that C/EBPβ has a cell-type specific role in the heart and that endogenous C/EBPβ in cardiomyocytes plays a salutary role during pressure overload.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"43 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089069","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}
Kamila Krol,Piotr Szczepaniak,Tomasz P Mikolajczyk
{"title":"ChemR23 signalling as a potential therapeutic target in atherosclerosis and cardiovascular diseases.","authors":"Kamila Krol,Piotr Szczepaniak,Tomasz P Mikolajczyk","doi":"10.1093/cvr/cvag037","DOIUrl":"https://doi.org/10.1093/cvr/cvag037","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"37 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073045","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}
Normal cardiac tissue glucose homeostasis is essential for the physiological function of the heart and the prevention of diabetic cardiomyopathies. The onset of diabetes mellitus has been reported to precede cardiovascular complications including cardiomyopathy, aortic stenosis, cardiac hypertrophy and hypertension. In addition to metabolic derangements, chronic medications such as HIV-antiretrovirals have also been associated with the risk factors of CVDs such as insulin resistance, dyslipidaemia, inflammation and oxidative stress and impaired glucose tolerance. Previous ART regimens have been associated with systemic insulin resistance and ectopic fat accumulation, leading to impaired glucose tolerance. The underlying molecular mechanisms behind the development of diabetic cardiomyopathies in persons chronically taking HIV-antiretrovirals remains unclear. Prediabetes is a condition of impaired glucose tolerance that is associated with low-grade inflammation and oxidative stress, which are precursors of CVDs. The link between chronic HIV-antiretroviral medication and prediabetes remains elusive. However, the increase in dispensation of HIV-antiretroviral medications has been associated with an increase in cases of prediabetes and diabetes, which could contribute to the development of CVDs. Hence, this review aims to provide insight into how the use of ARVs interacts with glucose metabolism and cardiovascular disease risk factors in patients on chronic HIV antiretrovirals.
{"title":"HIV-pharmacotherapy and pathogenesis of diabetes-induced cardiovascular complications: An updated narrative review.","authors":"Khanyisa Maswanganyi,Andile Khathi,Mlindeli Gamede","doi":"10.1093/cvr/cvag036","DOIUrl":"https://doi.org/10.1093/cvr/cvag036","url":null,"abstract":"Normal cardiac tissue glucose homeostasis is essential for the physiological function of the heart and the prevention of diabetic cardiomyopathies. The onset of diabetes mellitus has been reported to precede cardiovascular complications including cardiomyopathy, aortic stenosis, cardiac hypertrophy and hypertension. In addition to metabolic derangements, chronic medications such as HIV-antiretrovirals have also been associated with the risk factors of CVDs such as insulin resistance, dyslipidaemia, inflammation and oxidative stress and impaired glucose tolerance. Previous ART regimens have been associated with systemic insulin resistance and ectopic fat accumulation, leading to impaired glucose tolerance. The underlying molecular mechanisms behind the development of diabetic cardiomyopathies in persons chronically taking HIV-antiretrovirals remains unclear. Prediabetes is a condition of impaired glucose tolerance that is associated with low-grade inflammation and oxidative stress, which are precursors of CVDs. The link between chronic HIV-antiretroviral medication and prediabetes remains elusive. However, the increase in dispensation of HIV-antiretroviral medications has been associated with an increase in cases of prediabetes and diabetes, which could contribute to the development of CVDs. Hence, this review aims to provide insight into how the use of ARVs interacts with glucose metabolism and cardiovascular disease risk factors in patients on chronic HIV antiretrovirals.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"40 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088914","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":"Architects of decay: How fibroblast-like mesenchymal cells shape the necrotic core.","authors":"Yusuke Adachi,Alyssa Grogan,Aloke V Finn","doi":"10.1093/cvr/cvag025","DOIUrl":"https://doi.org/10.1093/cvr/cvag025","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"64 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056774","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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