{"title":"On the cusps of the second heart field: insights from zebrafish into arterial valve origins and disease.","authors":"Robert G Kelly","doi":"10.1093/cvr/cvae249","DOIUrl":"https://doi.org/10.1093/cvr/cvae249","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681055","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}
Karm A Alhasan, Melissa A King, Badal S B Pattar, Ian A Lewis, Gary D Lopaschuk, Steven C Greenway
Heart failure (HF) is a complex syndrome and a leading cause of mortality worldwide. While current medical treatment is based on known pathophysiology and is effective for many patients, the underlying cellular mechanisms are poorly understood. Energy deficiency is a characteristic of HF, marked by complex alterations in metabolism. Within the tricarboxylic acid cycle, anaplerosis emerges as an essential metabolic process responsible for replenishing lost intermediates, thereby playing a crucial role in sustaining energy metabolism and consequently cardiac function. Alterations in cardiac anaplerosis are commonly observed in HF, demonstrating potential for therapeutic intervention. This review discusses recent advances in understanding the anaplerotic adaptations that occur in HF. We also explore therapeutics that can directly modulate anaplerosis or are likely to confer cardioprotective effects through anaplerosis, which could potentially be implemented to rescue the failing heart.
{"title":"Anaplerotic filling in heart failure: a review of mechanism and potential therapeutics","authors":"Karm A Alhasan, Melissa A King, Badal S B Pattar, Ian A Lewis, Gary D Lopaschuk, Steven C Greenway","doi":"10.1093/cvr/cvae248","DOIUrl":"https://doi.org/10.1093/cvr/cvae248","url":null,"abstract":"Heart failure (HF) is a complex syndrome and a leading cause of mortality worldwide. While current medical treatment is based on known pathophysiology and is effective for many patients, the underlying cellular mechanisms are poorly understood. Energy deficiency is a characteristic of HF, marked by complex alterations in metabolism. Within the tricarboxylic acid cycle, anaplerosis emerges as an essential metabolic process responsible for replenishing lost intermediates, thereby playing a crucial role in sustaining energy metabolism and consequently cardiac function. Alterations in cardiac anaplerosis are commonly observed in HF, demonstrating potential for therapeutic intervention. This review discusses recent advances in understanding the anaplerotic adaptations that occur in HF. We also explore therapeutics that can directly modulate anaplerosis or are likely to confer cardioprotective effects through anaplerosis, which could potentially be implemented to rescue the failing heart.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"33 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684425","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":"TGF-β signalling: the Dr. Jekyll and Mr. Hyde of the aortic aneurysms.","authors":"Sara Perrotta, Daniela Carnevale, Giuseppe Lembo","doi":"10.1093/cvr/cvae245","DOIUrl":"https://doi.org/10.1093/cvr/cvae245","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675217","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}
Aims: We investigated whether the disruption of C-C motif chemokine receptor (CCR) 2 may attenuate the development of pulmonary arterial hypertension (PAH) in any rat models with the reversal of the associated pro-inflammatory state and vascular dysfunction, and synergize with a conventional pulmonary vasodilator.
Methods and results: Using Ccr2(-/-) rats generated by CRISPR/Cas9, we investigated pulmonary hypertension (PH) in Ccr2(+/+) or Ccr2(-/-) rats treated with monocrotaline (MCT), SU5416/hypoxia (SuHx) and chronic hypoxia (CH). Ccr2(-/-) decreased the right ventricular systolic pressure, an index of right ventricular hypertrophy and mortality rate, and reversed increased expression of inflammatory cytokines/chemokines (interleukin-6, tumor necrosis factor-α, C-C motif chemokine receptor (CCL)-2, interleukin-1β, transforming growth factor-β) in rats 3weeks after MCT injection, but not in SuHx or CH models. Consistently, Ccr2(-/-) decreased indices of pulmonary vascular diseases (PVD) and perivascular macrophage infiltration, as well as reversed impaired bone morphogenetic protein receptor type 2 signaling, increased endothelial apoptosis and impaired nitric oxide signaling and decreased phosphodiesterase-5 (PDE5) expression in lungs in MCT-treated rats. Gene expression of receptors for prostaglandin I2 and endothelin was not changed by Ccr2(-/-) in MCT-treated rats. In cultured pulmonary arterial smooth muscle cells (PASMCs), Ccr2(-/-) suppressed CCL2-induced hyperproliferation and dedifferentiation as well as reversed CCL2-induced decrease in PDE5 expression. The whole-genome RNA sequencing analysis identified differentially expressed genes in CCL2-stimulated Ccr2(-/-) PASMCs, which are related to regulation of cellular differentiation and contraction. Based on studies in rats and cultured PASMCs, we investigated whether a PDE5 inhibitor, tadalafil, synergizes with Ccr2(-/-). Tadalafil administration ameliorated PH and PVDs in MCT-treated Ccr2(-/-) rats but not in Ccr2(+/+) rats. Tadalafil further improved survival in MCT-treated Ccr2(-/-) rats.
Conclusion: The present findings demonstrated that CCR2 disruption ameliorated PAH in MCT-treated rats, which was associated with the reversal of dysregulated inflammatory pathways and vascular dysfunction and synergized with tadalafil. These findings suggest that CCR2 may be a therapeutic target in intractable PAH patients with a certain CCR2-related inflammatory phenotype and refractory to conventional pulmonary vasodilators.
{"title":"C-C motif chemokine receptor-2 blockade ameliorates pulmonary hypertension in rats and synergizes with a pulmonary vasodilator.","authors":"Naoki Tsuboya, Hirofumi Sawada, Yoshihide Mitani, Hironori Oshita, Kazunobu Ohya, Mami Takeoka, Jane Chanda Kabwe, Yoshiki Miyasaka, Hiromasa Ito, Noriko Yodoya, Hiroyuki Ohashi, Junko Maruyama, Ryuji Okamoto, Tomoji Mashimo, Kaoru Dohi, Yuhei Nishimura, Kazuo Maruyama, Masahiro Hirayama","doi":"10.1093/cvr/cvae244","DOIUrl":"https://doi.org/10.1093/cvr/cvae244","url":null,"abstract":"<p><strong>Aims: </strong>We investigated whether the disruption of C-C motif chemokine receptor (CCR) 2 may attenuate the development of pulmonary arterial hypertension (PAH) in any rat models with the reversal of the associated pro-inflammatory state and vascular dysfunction, and synergize with a conventional pulmonary vasodilator.</p><p><strong>Methods and results: </strong>Using Ccr2(-/-) rats generated by CRISPR/Cas9, we investigated pulmonary hypertension (PH) in Ccr2(+/+) or Ccr2(-/-) rats treated with monocrotaline (MCT), SU5416/hypoxia (SuHx) and chronic hypoxia (CH). Ccr2(-/-) decreased the right ventricular systolic pressure, an index of right ventricular hypertrophy and mortality rate, and reversed increased expression of inflammatory cytokines/chemokines (interleukin-6, tumor necrosis factor-α, C-C motif chemokine receptor (CCL)-2, interleukin-1β, transforming growth factor-β) in rats 3weeks after MCT injection, but not in SuHx or CH models. Consistently, Ccr2(-/-) decreased indices of pulmonary vascular diseases (PVD) and perivascular macrophage infiltration, as well as reversed impaired bone morphogenetic protein receptor type 2 signaling, increased endothelial apoptosis and impaired nitric oxide signaling and decreased phosphodiesterase-5 (PDE5) expression in lungs in MCT-treated rats. Gene expression of receptors for prostaglandin I2 and endothelin was not changed by Ccr2(-/-) in MCT-treated rats. In cultured pulmonary arterial smooth muscle cells (PASMCs), Ccr2(-/-) suppressed CCL2-induced hyperproliferation and dedifferentiation as well as reversed CCL2-induced decrease in PDE5 expression. The whole-genome RNA sequencing analysis identified differentially expressed genes in CCL2-stimulated Ccr2(-/-) PASMCs, which are related to regulation of cellular differentiation and contraction. Based on studies in rats and cultured PASMCs, we investigated whether a PDE5 inhibitor, tadalafil, synergizes with Ccr2(-/-). Tadalafil administration ameliorated PH and PVDs in MCT-treated Ccr2(-/-) rats but not in Ccr2(+/+) rats. Tadalafil further improved survival in MCT-treated Ccr2(-/-) rats.</p><p><strong>Conclusion: </strong>The present findings demonstrated that CCR2 disruption ameliorated PAH in MCT-treated rats, which was associated with the reversal of dysregulated inflammatory pathways and vascular dysfunction and synergized with tadalafil. These findings suggest that CCR2 may be a therapeutic target in intractable PAH patients with a certain CCR2-related inflammatory phenotype and refractory to conventional pulmonary vasodilators.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646878","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":"Inflammation and heart failure: are we facing a \"hedgehog's dilemma\"?","authors":"Stefano Ministrini, Giovanni G Camici","doi":"10.1093/cvr/cvae246","DOIUrl":"https://doi.org/10.1093/cvr/cvae246","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643714","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}
Juan Francisco Aranda, Cristina M Ramírez, María Mittelbrunn
Inflammaging, characterized by persistent chronic inflammation in older adults, has emerged as a critical factor linked to age-related diseases such as cardiovascular diseases (CVDs), metabolic disorders, and cognitive decline, which collectively contribute to the leading causes of death globally. Elevated levels of cytokines, chemokines, and others inflammatory mediators characterize inflammaging and serve as indicators of biological age. Among the causes of inflammaging, deterioration of the immune system, mitochondrial dysfunction, dysbiosis, accumulation of DAMPs, together with genetic or epigenetic factors, contribute to inflammaging not only in CVD but also in other age-related conditions. This review examines the causes and consequences of inflammaging, particularly its implications for atherosclerosis and heart failure with preserved ejection fraction (HFpEF) and explores potential strategies to mitigate it in the onset of CVD.
{"title":"Inflammaging, a targetable pathway for preventing cardiovascular diseases","authors":"Juan Francisco Aranda, Cristina M Ramírez, María Mittelbrunn","doi":"10.1093/cvr/cvae240","DOIUrl":"https://doi.org/10.1093/cvr/cvae240","url":null,"abstract":"Inflammaging, characterized by persistent chronic inflammation in older adults, has emerged as a critical factor linked to age-related diseases such as cardiovascular diseases (CVDs), metabolic disorders, and cognitive decline, which collectively contribute to the leading causes of death globally. Elevated levels of cytokines, chemokines, and others inflammatory mediators characterize inflammaging and serve as indicators of biological age. Among the causes of inflammaging, deterioration of the immune system, mitochondrial dysfunction, dysbiosis, accumulation of DAMPs, together with genetic or epigenetic factors, contribute to inflammaging not only in CVD but also in other age-related conditions. This review examines the causes and consequences of inflammaging, particularly its implications for atherosclerosis and heart failure with preserved ejection fraction (HFpEF) and explores potential strategies to mitigate it in the onset of CVD.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"95 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601208","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}
Yanhong Zhang, Xiaoxiao Yang, Mei Lan, Ze Yuan, Shuai Li, Yangping Liu, Cha Han, Ding Ai, Yang Yang, Yi Zhu, Bochuan Li
Aims Endothelial cells regulate vascular tone to control the blood pressure (BP) by producing both relaxing and contracting factors. Previously, we identified methyltransferase-like 3 (METTL3), a primary N6-methyladenosine (m6A) methyltransferase, as a key player in alleviating endothelial atherogenic progression. However, its involvement in BP regulation remains unclear. Methods and results To evaluate the role of METTL3 in vivo, mice with EC specific METTL3 deficiency (EC-Mettl3KO) with or without Ang II infusion were used to create a hypertensive model. Functional and MeRIP sequencing analysis were performed to explore the mechanism of METTL3-mediated hypertension. We observed a reduction in endothelial METTL3 activity by Ang II in vitro and in vivo. Endothelial METTL3-deficient mice exhibited higher BP than controls, with no gender disparity observed. The subsequent study primarily conducted in male mice. Through m6A sequencing and functional analysis, we identified m6A modification of various RUNX1 monomers resulted in endothelial dysfunction. Mutations in the 3′UTR region of RUNX1b abolished its luciferase reporter activity, and enhanced eNOS promoter luciferase reporter activity with or without METTL3 overexpression. Overexpression of METTL3 by adeno-associated virus reduced Ang II-induced BP elevation. Conclusion This study reveals that METTL3 alleviates hypertension through m6A-dependent stabilization of RUNX1b mRNA, leading to upregulation of eNOS, thus underscoring the pivotal role of RNA transcriptomics in the regulation of hypertension.
目的 内皮细胞通过产生松弛和收缩因子来调节血管张力，从而控制血压（BP）。此前，我们发现类似甲基转移酶 3（METTL3）是一种主要的 N6-甲基腺苷（m6A）甲基转移酶，是缓解内皮动脉粥样硬化进展的关键因素。然而，它参与血压调节的情况仍不清楚。方法和结果 为了评估 METTL3 在体内的作用，研究人员利用 EC 特异性 METTL3 缺乏（EC-Mettl3KO）的小鼠输注或不输注 Ang II 来创建高血压模型。为了探索METTL3介导高血压的机制，我们进行了功能和MeRIP测序分析。我们观察到 Ang II 在体外和体内降低了内皮 METTL3 的活性。内皮 METTL3 缺陷小鼠的血压高于对照组，但未观察到性别差异。随后的研究主要在雄性小鼠中进行。通过 m6A 测序和功能分析，我们发现各种 RUNX1 单体的 m6A 修饰导致了内皮功能障碍。RUNX1b的3′UTR区突变会取消其荧光素酶报告活性，而在METTL3过表达或不表达的情况下，eNOS启动子荧光素酶报告活性会增强。通过腺相关病毒过表达 METTL3 可降低 Ang II 诱导的血压升高。结论 本研究揭示了 METTL3 通过 m6A 依赖性稳定 RUNX1b mRNA，导致 eNOS 上调来缓解高血压，从而强调了 RNA 转录组学在高血压调控中的关键作用。
{"title":"Regulation of blood pressure by METTL3 via RUNX1b-eNOS pathway in endothelial cells in mice","authors":"Yanhong Zhang, Xiaoxiao Yang, Mei Lan, Ze Yuan, Shuai Li, Yangping Liu, Cha Han, Ding Ai, Yang Yang, Yi Zhu, Bochuan Li","doi":"10.1093/cvr/cvae242","DOIUrl":"https://doi.org/10.1093/cvr/cvae242","url":null,"abstract":"Aims Endothelial cells regulate vascular tone to control the blood pressure (BP) by producing both relaxing and contracting factors. Previously, we identified methyltransferase-like 3 (METTL3), a primary N6-methyladenosine (m6A) methyltransferase, as a key player in alleviating endothelial atherogenic progression. However, its involvement in BP regulation remains unclear. Methods and results To evaluate the role of METTL3 in vivo, mice with EC specific METTL3 deficiency (EC-Mettl3KO) with or without Ang II infusion were used to create a hypertensive model. Functional and MeRIP sequencing analysis were performed to explore the mechanism of METTL3-mediated hypertension. We observed a reduction in endothelial METTL3 activity by Ang II in vitro and in vivo. Endothelial METTL3-deficient mice exhibited higher BP than controls, with no gender disparity observed. The subsequent study primarily conducted in male mice. Through m6A sequencing and functional analysis, we identified m6A modification of various RUNX1 monomers resulted in endothelial dysfunction. Mutations in the 3′UTR region of RUNX1b abolished its luciferase reporter activity, and enhanced eNOS promoter luciferase reporter activity with or without METTL3 overexpression. Overexpression of METTL3 by adeno-associated virus reduced Ang II-induced BP elevation. Conclusion This study reveals that METTL3 alleviates hypertension through m6A-dependent stabilization of RUNX1b mRNA, leading to upregulation of eNOS, thus underscoring the pivotal role of RNA transcriptomics in the regulation of hypertension.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"80 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601201","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}
Giorgia Senesi, Alessandra M Lodrini, Shafeeq Mohammed, Simone Mosole, Jesper Hjortnaes, Rogier J A Veltrop, Bela Kubat, Davide Ceresa, Sara Bolis, Andrea Raimondi, Tiziano Torre, Paolo Malatesta, Marie-José Goumans, Francesco Paneni, Giovanni G Camici, Lucio Barile, Carolina Balbi, Giuseppe Vassalli
Background and Aims Cardiac fibrosis in response to injury leads to myocardial stiffness and heart failure. At the cellular level, fibrosis is triggered by the conversion of cardiac fibroblasts (CF) into extracellular matrix–producing myofibroblasts. miR-24-3p regulates this process in animal models. Here, we investigated whether miR-24-3p plays similar roles in human models. Methods and Results Gain– and loss–of–function experiments were performed using human induced pluripotent stem cell–derived cardiomyocytes (hCM) and primary hCF under normoxic or ischaemia–simulating conditions. hCM–derived extracellular vesicles (EVs) were added to hCF. Similar experiments were performed using three-dimensional human cardiac microtissues and ex vivo–cultured human cardiac slices. hCF transfection with miR-24-3p mimic prevented TGFβ1–mediated induction of FURIN, CCND1 and SMAD4—miR-24-3p target genes participating in TGFβ1–dependent fibrinogenesis —, regulating hCF–to–myofibroblast conversion. hCM secreted miR-24-3p as EV cargo. hCM–derived EVs modulated hCF activation. Ischaemia–simulating conditions induced miR-24-3p depletion in hCM-EVs and microtissues. Similarly, hypoxia downregulated miR-24-3p in cardiac slices. Analyses of clinical samples revealed decreased miR-24-3p levels in circulating EVs in acute myocardial infarction (AMI) patients, compared with healthy subjects. Post-mortem RNAScope analysis showed miR-24-3p downregulation in myocardium from AMI patients, compared with patients who died from noncardiac diseases. Berberin, a plant–derived agent with miR-24-3p–stimulatory activity, increased miR-24-3p contents in hCM-EVs, downregulated FURIN, CCND1 and SMAD4, and inhibited fibrosis in cardiac microtissues. Conclusions These findings suggest that hCM may control hCF activation through miR-24-3p secreted as EV cargo. Ischaemia impairs this mechanism, favouring fibrosis.
{"title":"miR-24-3p secreted as extracellular vesicle cargo by cardiomyocytes inhibits fibrosis in human cardiac microtissues","authors":"Giorgia Senesi, Alessandra M Lodrini, Shafeeq Mohammed, Simone Mosole, Jesper Hjortnaes, Rogier J A Veltrop, Bela Kubat, Davide Ceresa, Sara Bolis, Andrea Raimondi, Tiziano Torre, Paolo Malatesta, Marie-José Goumans, Francesco Paneni, Giovanni G Camici, Lucio Barile, Carolina Balbi, Giuseppe Vassalli","doi":"10.1093/cvr/cvae243","DOIUrl":"https://doi.org/10.1093/cvr/cvae243","url":null,"abstract":"Background and Aims Cardiac fibrosis in response to injury leads to myocardial stiffness and heart failure. At the cellular level, fibrosis is triggered by the conversion of cardiac fibroblasts (CF) into extracellular matrix–producing myofibroblasts. miR-24-3p regulates this process in animal models. Here, we investigated whether miR-24-3p plays similar roles in human models. Methods and Results Gain– and loss–of–function experiments were performed using human induced pluripotent stem cell–derived cardiomyocytes (hCM) and primary hCF under normoxic or ischaemia–simulating conditions. hCM–derived extracellular vesicles (EVs) were added to hCF. Similar experiments were performed using three-dimensional human cardiac microtissues and ex vivo–cultured human cardiac slices. hCF transfection with miR-24-3p mimic prevented TGFβ1–mediated induction of FURIN, CCND1 and SMAD4—miR-24-3p target genes participating in TGFβ1–dependent fibrinogenesis —, regulating hCF–to–myofibroblast conversion. hCM secreted miR-24-3p as EV cargo. hCM–derived EVs modulated hCF activation. Ischaemia–simulating conditions induced miR-24-3p depletion in hCM-EVs and microtissues. Similarly, hypoxia downregulated miR-24-3p in cardiac slices. Analyses of clinical samples revealed decreased miR-24-3p levels in circulating EVs in acute myocardial infarction (AMI) patients, compared with healthy subjects. Post-mortem RNAScope analysis showed miR-24-3p downregulation in myocardium from AMI patients, compared with patients who died from noncardiac diseases. Berberin, a plant–derived agent with miR-24-3p–stimulatory activity, increased miR-24-3p contents in hCM-EVs, downregulated FURIN, CCND1 and SMAD4, and inhibited fibrosis in cardiac microtissues. Conclusions These findings suggest that hCM may control hCF activation through miR-24-3p secreted as EV cargo. Ischaemia impairs this mechanism, favouring fibrosis.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"29 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599703","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":"Correction to: Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.","authors":"","doi":"10.1093/cvr/cvae233","DOIUrl":"https://doi.org/10.1093/cvr/cvae233","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589605","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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