Bo-Ram Jin,Tripti Kumari,Jingu Lee,Jae-Sung Kim,Radka Bokorova,Atish Gheware,Carla Valenzuela Ripoll,Alireza Sargazi,Soi Jeong,Young-Min Hyun,Sana Saif Ur Rehman,Babak Razani,Janet S Lee,Ali Javaheri,Jaehyung Cho
AIMSSodium-glucose co-transporter 2 inhibitors are widely used to treat patients with type 2 diabetes and exhibit beneficial cardiovascular effects beyond glucose lowering. In this study, we investigated their potential to alleviate vaso-occlusive events and organ damage in sickle cell disease (SCD) mice.METHODS AND RESULTSIntravital and immunofluorescence microscopy reveal that 4-day oral administration of dapagliflozin (DAPA) or sotagliflozin (SOTA) significantly reduces neutrophil adhesion and transmigration in cremaster venules, with SOTA showing greater inhibition, and downregulates E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression in cremaster venules of TNF-α-challenged SCD mice. Intriguingly, only SOTA improves mouse survival acutely. Similar inhibitory effects on neutrophil recruitment are observed in SCD mice subjected to hypoxia-reoxygenation. Flow chamber assays indicate that neither drug directly affects neutrophil or endothelial cell adhesive function. In addition, treatment of neutrophils and platelets from SCD mice and patients with DAPA or SOTA does not affect their activation. When administered for 4 months, DAPA or SOTA mitigates neutrophil recruitment and enhances microcirculation in cremaster venules of TNF-α-challenged SCD mice, while only SOTA confers a survival benefit. Both drugs reduce leukocyte infiltration in the liver or lungs, suggesting their ability to protect against organ damage. Co-administration with hydroxyurea for 4 months does not enhance these effects. Multiplex analysis shows that DAPA and SOTA lower plasma levels of soluble P-selectin, ICAM-1, S100A8/A9, and pro-inflammatory cytokines in SCD mice.CONCLUSIONSOur findings suggest that DAPA and SOTA mitigate vaso-occlusive events in SCD, with SOTA providing superior benefits.TRANSLATIONAL PERSPECTIVESickle cell disease (SCD) is an inherited autosomal recessive disorder characterized by red blood cell hymolysis, oxidative stress, and chronic inflammation. Recurrent vaso-occlusive crises driven by intravascular cell-cell adhesion and aggregation and the hallmark of SCD. In this study, we show that dapagliflozing (DAPA), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), and sotagliflozin (SOTA), an SGLT1/2i, reduce acute vaso-occlusion in SCD mice subjected to severe inflammation or hypoxia-reoxygenation, with SOTA providing greater benefit.These findings suggest that SGLT2 or SGLT1/2 inhibition may help attenuate vaso-occlusive pain crises in SCD patients.
{"title":"Beneficial effects of SGLT1/2 and SGLT2 inhibitors on vaso-occlusive events and organ damage in sickle cell disease mice.","authors":"Bo-Ram Jin,Tripti Kumari,Jingu Lee,Jae-Sung Kim,Radka Bokorova,Atish Gheware,Carla Valenzuela Ripoll,Alireza Sargazi,Soi Jeong,Young-Min Hyun,Sana Saif Ur Rehman,Babak Razani,Janet S Lee,Ali Javaheri,Jaehyung Cho","doi":"10.1093/cvr/cvag003","DOIUrl":"https://doi.org/10.1093/cvr/cvag003","url":null,"abstract":"AIMSSodium-glucose co-transporter 2 inhibitors are widely used to treat patients with type 2 diabetes and exhibit beneficial cardiovascular effects beyond glucose lowering. In this study, we investigated their potential to alleviate vaso-occlusive events and organ damage in sickle cell disease (SCD) mice.METHODS AND RESULTSIntravital and immunofluorescence microscopy reveal that 4-day oral administration of dapagliflozin (DAPA) or sotagliflozin (SOTA) significantly reduces neutrophil adhesion and transmigration in cremaster venules, with SOTA showing greater inhibition, and downregulates E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression in cremaster venules of TNF-α-challenged SCD mice. Intriguingly, only SOTA improves mouse survival acutely. Similar inhibitory effects on neutrophil recruitment are observed in SCD mice subjected to hypoxia-reoxygenation. Flow chamber assays indicate that neither drug directly affects neutrophil or endothelial cell adhesive function. In addition, treatment of neutrophils and platelets from SCD mice and patients with DAPA or SOTA does not affect their activation. When administered for 4 months, DAPA or SOTA mitigates neutrophil recruitment and enhances microcirculation in cremaster venules of TNF-α-challenged SCD mice, while only SOTA confers a survival benefit. Both drugs reduce leukocyte infiltration in the liver or lungs, suggesting their ability to protect against organ damage. Co-administration with hydroxyurea for 4 months does not enhance these effects. Multiplex analysis shows that DAPA and SOTA lower plasma levels of soluble P-selectin, ICAM-1, S100A8/A9, and pro-inflammatory cytokines in SCD mice.CONCLUSIONSOur findings suggest that DAPA and SOTA mitigate vaso-occlusive events in SCD, with SOTA providing superior benefits.TRANSLATIONAL PERSPECTIVESickle cell disease (SCD) is an inherited autosomal recessive disorder characterized by red blood cell hymolysis, oxidative stress, and chronic inflammation. Recurrent vaso-occlusive crises driven by intravascular cell-cell adhesion and aggregation and the hallmark of SCD. In this study, we show that dapagliflozing (DAPA), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), and sotagliflozin (SOTA), an SGLT1/2i, reduce acute vaso-occlusion in SCD mice subjected to severe inflammation or hypoxia-reoxygenation, with SOTA providing greater benefit.These findings suggest that SGLT2 or SGLT1/2 inhibition may help attenuate vaso-occlusive pain crises in SCD patients.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"16 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961455","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}
Aim Ischemic heart disease is a leading cause of death worldwide, and heart failure after myocardial infarction (MI) is a growing issue in an ageing society. Macrophages play a central role in left ventricular (LV) remodeling after MI. Mitochondria consistently change their morphology, including fission and fusion; however, the role of these morphological changes, particularly in macrophages, remains unknown. This study investigated the role of dynamin-related protein 1 (Drp1), a key mediator of mitochondrial fission, in macrophages and its involvement in the mechanisms of left ventricular remodeling after myocardial infarction (MI). Methods and Results This study utilized genetically altered mice lacking Drp1 in Lysozyme M-positive cells (Drp1-KO) to elucidate the specific role of macrophage Drp1 in post-infarct LV remodeling. Deletion of Drp1 in macrophages exacerbated LV remodeling, underpinned by reduced ejection fraction and increased LV diameter, which resulted in a poor prognosis after MI. Histological analysis indicated increased fibrosis and sustained macrophage accumulation in the infarcted hearts of Drp1-KO mice. Blockade of Drp1 in macrophages decreased mitochondrial fission and impaired mitophagy, leading to the subsequent release of mitochondrial DNA (mtDNA) into the cytosol and the induction of inflammatory cytokines. This induction was abrogated by the autophagy inducer Tat-beclin1 or siRNA-mediated knockdown of Z-DNA Binding Protein 1 (ZBP1). Deletion of ZBP1 in bone marrow-derived cells abrogated LV remodeling induced by the Drp1 inhibitor Mdivi-1. Conclusion Macrophage Drp1 plays a critical role in the pathobiology of post-infarct LV remodeling, particularly in mitochondrial quality control mechanisms. Macrophage Drp1 could be a novel therapeutic molecule to mitigate the progression of LV remodeling and consequent heart failure after MI.
{"title":"Drp1-mediated mitochondrial fission protects macrophages from mtDNA/ZBP1-mediated inflammation and inhibits post-infarct cardiac remodeling","authors":"Yuki Kondo, Jun-ichiro Koga, Nasanbadrakh Orkhonselenge, Lixiang Wang, Nao Hasuzawa, Shunsuke Katsuki, Tetsuya Matoba, Yosuke Nishimura, Masatoshi Nomura, Masaharu Kataoka","doi":"10.1093/cvr/cvag006","DOIUrl":"https://doi.org/10.1093/cvr/cvag006","url":null,"abstract":"Aim Ischemic heart disease is a leading cause of death worldwide, and heart failure after myocardial infarction (MI) is a growing issue in an ageing society. Macrophages play a central role in left ventricular (LV) remodeling after MI. Mitochondria consistently change their morphology, including fission and fusion; however, the role of these morphological changes, particularly in macrophages, remains unknown. This study investigated the role of dynamin-related protein 1 (Drp1), a key mediator of mitochondrial fission, in macrophages and its involvement in the mechanisms of left ventricular remodeling after myocardial infarction (MI). Methods and Results This study utilized genetically altered mice lacking Drp1 in Lysozyme M-positive cells (Drp1-KO) to elucidate the specific role of macrophage Drp1 in post-infarct LV remodeling. Deletion of Drp1 in macrophages exacerbated LV remodeling, underpinned by reduced ejection fraction and increased LV diameter, which resulted in a poor prognosis after MI. Histological analysis indicated increased fibrosis and sustained macrophage accumulation in the infarcted hearts of Drp1-KO mice. Blockade of Drp1 in macrophages decreased mitochondrial fission and impaired mitophagy, leading to the subsequent release of mitochondrial DNA (mtDNA) into the cytosol and the induction of inflammatory cytokines. This induction was abrogated by the autophagy inducer Tat-beclin1 or siRNA-mediated knockdown of Z-DNA Binding Protein 1 (ZBP1). Deletion of ZBP1 in bone marrow-derived cells abrogated LV remodeling induced by the Drp1 inhibitor Mdivi-1. Conclusion Macrophage Drp1 plays a critical role in the pathobiology of post-infarct LV remodeling, particularly in mitochondrial quality control mechanisms. Macrophage Drp1 could be a novel therapeutic molecule to mitigate the progression of LV remodeling and consequent heart failure after MI.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"29 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986321","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}
Yingxi Li,Razoan Al Rimon,Faqi Wang,Haoyang Li,Slava Epelman,Michelle D Tallquist,Lindsey Westover,Gavin Y Oudit,Zamaneh Kassiri
AIMSMyocardial infarction (MI) triggers a complex remodeling that, if uncontrolled, leads to heart failure. Increased levels of ADAM17 (disintegrin and metalloproteinase-17) in ischemic injury has been reported, but its direct role in scar formation and subsequent recovery from MI has not been identified. We investigated the role of ADAM17 in the function of homeostatic fibroblasts (FBs) vs. activated myofibroblasts (myoFBs) in scar formation, and recovery following MI.METHODS AND RESULTSHuman myocardial specimens showed upregulated ADAM17 in the infarct tissue, colocalized to myofibroblasts. We generated two inducible genetic mouse models with Adam17 knockdown in FBs (Adam17FB-KD) or myoFB (Adam17myoFB-KD) and subjected them to MI. Loss of ADAM17 in FBs impaired infarct formation and increased mortality due to left ventricular (LV) rupture in males and females. In contrast, ADAM17 loss in myoFBs limited infarct expansion, LV dilation and dysfunction up to 4-wks post-MI. Macrophage infiltration was suppressed in both genotypes. Ex vivo and in vitro experiments revealed that loss of ADAM17 in myoFB resulted in scar tissue with reduced stiffness due to suppressed activation of epidermal growth factor receptor and the Yes-associated protein (YAP) pathway. This promoted VEGFR signaling, endothelial cell (EC) proliferation, and vascularization in the infarcted myocardium, limiting infarct expansion. RNAseq analyses showed drastic changes in extracellular matrix (ECM) genes in Adam17KD FB and myoFBs in hypoxia. In vitro co-culture of myoFB and ECs confirmed that the ECM deposited by Adam17-deficient myoFB promotes EC proliferation and sprouting. Pharmacological inhibition of ADAM17 before MI was ineffective, but short-term ADAM17 inhibition after MI (targeting the myoFBs), limited infarct expansion, LV dilation and dysfunction up to 4-weeks post-MI.CONCLUSIONShort-term inhibition of ADAM17 after MI optimizes the compliance of the infarct tissue, promoting vascularization, limiting infarct expansion, preventing long-term adverse LV remodeling, dysfunction, and heart failure. Targeting the homeostatic FB vs. myoFB also highlights the critical timing of ADAM17 inhibition as its presence is essential for the initial healing of the infarcted heart, but inhibition of its persistent upregulation reduces scar stiffness and improves the outcome post-MI.
{"title":"Temporal inhibition of ADAM17 in fibroblasts reduces stiffness and promotes vascularization following myocardial infarction.","authors":"Yingxi Li,Razoan Al Rimon,Faqi Wang,Haoyang Li,Slava Epelman,Michelle D Tallquist,Lindsey Westover,Gavin Y Oudit,Zamaneh Kassiri","doi":"10.1093/cvr/cvaf256","DOIUrl":"https://doi.org/10.1093/cvr/cvaf256","url":null,"abstract":"AIMSMyocardial infarction (MI) triggers a complex remodeling that, if uncontrolled, leads to heart failure. Increased levels of ADAM17 (disintegrin and metalloproteinase-17) in ischemic injury has been reported, but its direct role in scar formation and subsequent recovery from MI has not been identified. We investigated the role of ADAM17 in the function of homeostatic fibroblasts (FBs) vs. activated myofibroblasts (myoFBs) in scar formation, and recovery following MI.METHODS AND RESULTSHuman myocardial specimens showed upregulated ADAM17 in the infarct tissue, colocalized to myofibroblasts. We generated two inducible genetic mouse models with Adam17 knockdown in FBs (Adam17FB-KD) or myoFB (Adam17myoFB-KD) and subjected them to MI. Loss of ADAM17 in FBs impaired infarct formation and increased mortality due to left ventricular (LV) rupture in males and females. In contrast, ADAM17 loss in myoFBs limited infarct expansion, LV dilation and dysfunction up to 4-wks post-MI. Macrophage infiltration was suppressed in both genotypes. Ex vivo and in vitro experiments revealed that loss of ADAM17 in myoFB resulted in scar tissue with reduced stiffness due to suppressed activation of epidermal growth factor receptor and the Yes-associated protein (YAP) pathway. This promoted VEGFR signaling, endothelial cell (EC) proliferation, and vascularization in the infarcted myocardium, limiting infarct expansion. RNAseq analyses showed drastic changes in extracellular matrix (ECM) genes in Adam17KD FB and myoFBs in hypoxia. In vitro co-culture of myoFB and ECs confirmed that the ECM deposited by Adam17-deficient myoFB promotes EC proliferation and sprouting. Pharmacological inhibition of ADAM17 before MI was ineffective, but short-term ADAM17 inhibition after MI (targeting the myoFBs), limited infarct expansion, LV dilation and dysfunction up to 4-weeks post-MI.CONCLUSIONShort-term inhibition of ADAM17 after MI optimizes the compliance of the infarct tissue, promoting vascularization, limiting infarct expansion, preventing long-term adverse LV remodeling, dysfunction, and heart failure. Targeting the homeostatic FB vs. myoFB also highlights the critical timing of ADAM17 inhibition as its presence is essential for the initial healing of the infarcted heart, but inhibition of its persistent upregulation reduces scar stiffness and improves the outcome post-MI.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"21 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949714","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}
Milène Freneau, Raphael Blanchet, Maxence Bodet, Sandro Benichi, Mary-Adel Mrad, Surya Prakash Rao Batta, Marc Rio, Stéphanie Bonnaud, Pierre Lindenbaum, Fabien Laporte, Stéphane Cuénot, Thibaud Quillard, Mike Maillasson, Sandrine Morel, Brenda Kwak, Philippe Bijlenga, Jean-François Deleuze, Christian Dina, Stéphanie Chatel, Emmanuelle Bourcereau, Solène Jouan, Arturo Consoli, Cyril Dargazanli, Julien Ognard, Hubert Desal, Anne-Clémence Vion, Romain Bourcier, Gervaise Loirand, Richard Redon
Aims Intracranial aneurysm (IA) is a common cerebrovascular abnormality characterized by localized dilation and wall thinning in cerebral arteries, which can rupture and lead to fatal subarachnoid hemorrhage. Although genetic factors can contribute to IA, the genetic predisposition of IA is largely unknown. This study aims to identify rare functional variants associated with IA in families with multiple affected subjects and explore their impact on IA pathophysiology. Methods and results By combining whole exome sequencing and identity-by-descent analyses, we have identified two rare missense variants in the CTSO gene associated to IA in two large families with multiple affected subjects. We found that the cysteine-type papain-like cathepsin O (CTSO) encoded by CTSO is expressed in the circle of Willis of mice and in the wall of human IA domes. Stretching of vascular smooth muscle cells (VSMC) induced CTSO secretion. CTSO controls VSMC migration and adhesion to the extracellular matrix, and directly interacts with fibronectin (FN). CTSO depletion, or expression of the two CTSO variants, which are poorly secreted, increased the amount of FN. Moreover, CTSO depletion augmented VSMC stiffness, which was reduced by the addition of exogenous CTSO. Conclusion Collectively, our findings identify CTSO as a potential new player in arterial remodeling, regulating FN deposition and VSMC function, supporting the causal role of rare coding CTSO variants in familial forms of IA.
{"title":"Identification of rare missense variants reducing cathepsin O secretion in families with intracranial aneurysm","authors":"Milène Freneau, Raphael Blanchet, Maxence Bodet, Sandro Benichi, Mary-Adel Mrad, Surya Prakash Rao Batta, Marc Rio, Stéphanie Bonnaud, Pierre Lindenbaum, Fabien Laporte, Stéphane Cuénot, Thibaud Quillard, Mike Maillasson, Sandrine Morel, Brenda Kwak, Philippe Bijlenga, Jean-François Deleuze, Christian Dina, Stéphanie Chatel, Emmanuelle Bourcereau, Solène Jouan, Arturo Consoli, Cyril Dargazanli, Julien Ognard, Hubert Desal, Anne-Clémence Vion, Romain Bourcier, Gervaise Loirand, Richard Redon","doi":"10.1093/cvr/cvaf279","DOIUrl":"https://doi.org/10.1093/cvr/cvaf279","url":null,"abstract":"Aims Intracranial aneurysm (IA) is a common cerebrovascular abnormality characterized by localized dilation and wall thinning in cerebral arteries, which can rupture and lead to fatal subarachnoid hemorrhage. Although genetic factors can contribute to IA, the genetic predisposition of IA is largely unknown. This study aims to identify rare functional variants associated with IA in families with multiple affected subjects and explore their impact on IA pathophysiology. Methods and results By combining whole exome sequencing and identity-by-descent analyses, we have identified two rare missense variants in the CTSO gene associated to IA in two large families with multiple affected subjects. We found that the cysteine-type papain-like cathepsin O (CTSO) encoded by CTSO is expressed in the circle of Willis of mice and in the wall of human IA domes. Stretching of vascular smooth muscle cells (VSMC) induced CTSO secretion. CTSO controls VSMC migration and adhesion to the extracellular matrix, and directly interacts with fibronectin (FN). CTSO depletion, or expression of the two CTSO variants, which are poorly secreted, increased the amount of FN. Moreover, CTSO depletion augmented VSMC stiffness, which was reduced by the addition of exogenous CTSO. Conclusion Collectively, our findings identify CTSO as a potential new player in arterial remodeling, regulating FN deposition and VSMC function, supporting the causal role of rare coding CTSO variants in familial forms of IA.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"43 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920328","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":"Is it the extracellular matrix?-smooth muscle fate in pulmonary hypertension secondary to left heart disease.","authors":"Oleg Pak,Norbert Weissmann","doi":"10.1093/cvr/cvaf261","DOIUrl":"https://doi.org/10.1093/cvr/cvaf261","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"123 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907761","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":"Trained immunity links cardiovascular disease and COVID-19.","authors":"Jéssica C Dos Santos,Mihai G Netea,Niels P Riksen","doi":"10.1093/cvr/cvaf278","DOIUrl":"https://doi.org/10.1093/cvr/cvaf278","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"42 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903696","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}
Jaideep Singh, Christopher Peter Stanley, Mary Meltem Kavurma
Mitochondria are essential organelles that generate adenosine triphosphate during oxidative phosphorylation by the electron transport chain. Beyond energy production, mitochondria regulate intracellular calcium homeostasis, generate signalling molecules, modulate metabolic pathways, and control cell survival. Mitochondrial dysfunction is characterised by excessive reactive oxygen species production, loss of membrane potential, calcium leakage, and structural abnormalities, ultimately lead to cell death. In endothelial cells, mitochondrial dysfunction drives endothelial impairment and contributes to cardiovascular diseases. This review explores the mechanisms underlying endothelial mitochondrial dysfunction and examines its role in the development and progression of hypertension, atherosclerosis, and diabetes.
{"title":"Endothelial mitochondrial dysfunction in hypertension, diabetes and atherosclerosis","authors":"Jaideep Singh, Christopher Peter Stanley, Mary Meltem Kavurma","doi":"10.1093/cvr/cvaf282","DOIUrl":"https://doi.org/10.1093/cvr/cvaf282","url":null,"abstract":"Mitochondria are essential organelles that generate adenosine triphosphate during oxidative phosphorylation by the electron transport chain. Beyond energy production, mitochondria regulate intracellular calcium homeostasis, generate signalling molecules, modulate metabolic pathways, and control cell survival. Mitochondrial dysfunction is characterised by excessive reactive oxygen species production, loss of membrane potential, calcium leakage, and structural abnormalities, ultimately lead to cell death. In endothelial cells, mitochondrial dysfunction drives endothelial impairment and contributes to cardiovascular diseases. This review explores the mechanisms underlying endothelial mitochondrial dysfunction and examines its role in the development and progression of hypertension, atherosclerosis, and diabetes.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"22 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903701","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":"Abstract writing in the modern era of artificial intelligence.","authors":"Kenneth Chan, Pok-Tin Tang","doi":"10.1093/cvr/cvaf253","DOIUrl":"https://doi.org/10.1093/cvr/cvaf253","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"121 17","pages":"2611-2613"},"PeriodicalIF":13.3,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862331","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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