首页 > 最新文献

Journal of molecular and cellular cardiology最新文献

英文 中文
Long noncoding RNA VENTHEART is required for ventricular cardiomyocyte specification and function 长非编码 RNA VENTHEART 是心室心肌细胞规格和功能的必要条件
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-28 DOI: 10.1016/j.yjmcc.2024.10.009
Yiqing Yang , Albert Dashi , Poh Loong Soong , Kun Han Lin , Wilson L.W. Tan , Bangfen Pan , Matias I. Autio , Zenia Tiang , Robin J.G. Hartman , Heming Wei , Matthew Andrew Ackers-Johnson , Bing Lim , Anna Walentinsson , Vidhya Vardharajan Iyer , Malin K.B. Jonsson , Roger S. Foo

Rationale

Cardiac-expressed long noncoding RNAs (lncRNAs) are important for cardiomyocyte (CM) differentiation and function. Several lncRNAs have been identified and characterized for early CM lineage commitment, however those in later CM lineage specification and maturation remain less well studied. Moreover, unique atrial / ventricular lncRNA expression has never been studied in detail.

Objectives

Here, we characterized a novel ventricular myocyte-restricted lncRNA, not expressed in atrial myocytes, and conserved only in primates.

Methods and results

First, we performed single cell RNA-seq on human pluripotent stem cell derived cardiomyocytes (hPSC-CM) at the late stages of 2, 6 and 12 weeks of differentiation. Weighted correlation network analysis identified core gene modules, including a set of lncRNAs highly abundant and predominantly expressed in the human heart. A lncRNA (we call VENTHEART, VHRT) co-expressed with cardiac maturation and ventricular-specific genes MYL2 and MYH7, and was expressed in fetal and adult human ventricles, but not atria. CRISPR-mediated deletion of the VHRT gene led to impaired CM sarcomere formation and significant disruption of the ventricular CM gene program. Indeed, a similar disruption was not observed in VHRT KO hPSC-derived atrial CM, suggesting that VHRT exhibits only ventricular myocyte subtype-specific effects. Optical recordings validated that loss of VHRT significantly prolonged action potential duration at 90 % repolarization (APD90) for ventricular-like, but not atrial-like, CMs.

Conclusion

This reports the first lncRNA that is exclusively required for proper ventricular, and not atrial, CM specification and function.
理由:心脏表达的长非编码 RNA(lncRNA)对心肌细胞(CM)的分化和功能非常重要。目前已发现并鉴定了几种与早期心肌细胞谱系定向有关的 lncRNA,但对后期心肌细胞谱系定向和成熟过程中的 lncRNA 的研究仍然较少。方法与结果首先,我们对人多能干细胞衍生的心肌细胞(hPSC-CM)在分化后期2周、6周和12周进行了单细胞RNA-seq分析。加权相关网络分析确定了核心基因模块,包括一组在人类心脏中高度丰富且主要表达的lncRNA。一种lncRNA(我们称之为VENTHEART,VHRT)与心脏成熟和心室特异基因MYL2和MYH7共表达,在胎儿和成人心室中表达,但不在心房中表达。CRISPR 介导的 VHRT 基因缺失会导致 CM 肌节形成受损,并显著破坏心室 CM 基因程序。事实上,在 VHRT KO hPSC 衍生的心房 CM 中并未观察到类似的破坏,这表明 VHRT 只表现出心室肌细胞亚型特异性的影响。光学记录验证了 VHRT 的缺失会显著延长类心室而非类心房 CM 90% 复极时的动作电位持续时间(APD90)。
{"title":"Long noncoding RNA VENTHEART is required for ventricular cardiomyocyte specification and function","authors":"Yiqing Yang ,&nbsp;Albert Dashi ,&nbsp;Poh Loong Soong ,&nbsp;Kun Han Lin ,&nbsp;Wilson L.W. Tan ,&nbsp;Bangfen Pan ,&nbsp;Matias I. Autio ,&nbsp;Zenia Tiang ,&nbsp;Robin J.G. Hartman ,&nbsp;Heming Wei ,&nbsp;Matthew Andrew Ackers-Johnson ,&nbsp;Bing Lim ,&nbsp;Anna Walentinsson ,&nbsp;Vidhya Vardharajan Iyer ,&nbsp;Malin K.B. Jonsson ,&nbsp;Roger S. Foo","doi":"10.1016/j.yjmcc.2024.10.009","DOIUrl":"10.1016/j.yjmcc.2024.10.009","url":null,"abstract":"<div><h3>Rationale</h3><div>Cardiac-expressed long noncoding RNAs (lncRNAs) are important for cardiomyocyte (CM) differentiation and function. Several lncRNAs have been identified and characterized for early CM lineage commitment, however those in later CM lineage specification and maturation remain less well studied. Moreover, unique atrial / ventricular lncRNA expression has never been studied in detail.</div></div><div><h3>Objectives</h3><div>Here, we characterized a novel ventricular myocyte-restricted lncRNA, not expressed in atrial myocytes, and conserved only in primates.</div></div><div><h3>Methods and results</h3><div>First, we performed single cell RNA-seq on human pluripotent stem cell derived cardiomyocytes (hPSC-CM) at the late stages of 2, 6 and 12 weeks of differentiation. Weighted correlation network analysis identified core gene modules, including a set of lncRNAs highly abundant and predominantly expressed in the human heart. A lncRNA (we call <em>VENTHEART</em>, <em>VHRT</em>) co-expressed with cardiac maturation and ventricular-specific genes <em>MYL2</em> and <em>MYH7</em>, and was expressed in fetal and adult human ventricles, but not atria. CRISPR-mediated deletion of the <em>VHRT</em> gene led to impaired CM sarcomere formation and significant disruption of the ventricular CM gene program. Indeed, a similar disruption was not observed in <em>VHRT</em> KO hPSC-derived atrial CM, suggesting that <em>VHRT</em> exhibits only ventricular myocyte subtype-specific effects. Optical recordings validated that loss of <em>VHRT</em> significantly prolonged action potential duration at 90 % repolarization (APD<sub>90</sub>) for ventricular-like, but not atrial-like, CMs.</div></div><div><h3>Conclusion</h3><div>This reports the first lncRNA that is exclusively required for proper ventricular, and not atrial, CM specification and function.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 90-102"},"PeriodicalIF":4.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human sclerostin gene expression is associated with asymptomatic carotid atherosclerosis and plaque stability features 人类硬骨蛋白基因表达与无症状颈动脉粥样硬化和斑块稳定性特征有关。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-24 DOI: 10.1016/j.yjmcc.2024.10.010
Anna Meryn , Andreas Edsfeldt , Jiangming Sun , Ana Persson , Isabel Gonçalves , Annelie Shami
{"title":"Human sclerostin gene expression is associated with asymptomatic carotid atherosclerosis and plaque stability features","authors":"Anna Meryn ,&nbsp;Andreas Edsfeldt ,&nbsp;Jiangming Sun ,&nbsp;Ana Persson ,&nbsp;Isabel Gonçalves ,&nbsp;Annelie Shami","doi":"10.1016/j.yjmcc.2024.10.010","DOIUrl":"10.1016/j.yjmcc.2024.10.010","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 59-60"},"PeriodicalIF":4.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of cardiomyocyte neddylation impairs embryonic cardiac morphogenesis 抑制心肌细胞的 Neddylation 会损害胚胎心脏的形态发生。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-20 DOI: 10.1016/j.yjmcc.2024.10.006
Rodney Littlejohn , Josue Zambrano-Carrasco , Jianqiu Zou , Yali Yao , Il-man Kim , Jiliang Zhou , Jie Li , Huabo Su
Heart development is a complex spatiotemporal process involving a series of orchestrated morphogenic events that result in the formation of an efficient pumping organ. How posttranslational mechanisms regulate heart development remains poorly understood. Therefore, we investigate how neddylation, the attachment of NEDD8 to target proteins, coordinates cardiogenesis. Abrogation of neddylation by deleting Nae1 in the heart via Sm22αCre led to early embryonic lethality. Mutant hearts exhibited deficits in trabeculation and expansion of the compact layer due to reduced cardiomyocyte proliferation, which was linked to abnormal Notch signaling in the developing heart. Overall, our findings demonstrate an essential role for neddylation in cardiogenesis.
心脏的发育是一个复杂的时空过程,涉及一系列精心策划的形态发生事件,最终形成一个高效的泵器官。人们对翻译后机制如何调控心脏发育仍然知之甚少。因此,我们研究了neddylation(NEDD8与靶蛋白的连接)如何协调心脏的发生。通过Sm22αCre基因在心脏中删除Nae1来削弱neddylation,导致早期胚胎死亡。由于心肌细胞增殖减少,突变体心脏显示出小梁和致密层扩张的缺陷,这与发育中心脏的Notch信号异常有关。总之,我们的研究结果证明了neddylation在心脏发生过程中的重要作用。
{"title":"Inhibition of cardiomyocyte neddylation impairs embryonic cardiac morphogenesis","authors":"Rodney Littlejohn ,&nbsp;Josue Zambrano-Carrasco ,&nbsp;Jianqiu Zou ,&nbsp;Yali Yao ,&nbsp;Il-man Kim ,&nbsp;Jiliang Zhou ,&nbsp;Jie Li ,&nbsp;Huabo Su","doi":"10.1016/j.yjmcc.2024.10.006","DOIUrl":"10.1016/j.yjmcc.2024.10.006","url":null,"abstract":"<div><div>Heart development is a complex spatiotemporal process involving a series of orchestrated morphogenic events that result in the formation of an efficient pumping organ. How posttranslational mechanisms regulate heart development remains poorly understood. Therefore, we investigate how neddylation, the attachment of NEDD8 to target proteins, coordinates cardiogenesis. Abrogation of neddylation by deleting <em>Nae1</em> in the heart via <em>Sm22α</em><sup><em>Cre</em></sup> led to early embryonic lethality. Mutant hearts exhibited deficits in trabeculation and expansion of the compact layer due to reduced cardiomyocyte proliferation, which was linked to abnormal Notch signaling in the developing heart. Overall, our findings demonstrate an essential role for neddylation in cardiogenesis.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 40-44"},"PeriodicalIF":4.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stochastic and alternating pacing paradigms to assess the stability of cardiac conduction 评估心脏传导稳定性的随机和交替起搏范例。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-20 DOI: 10.1016/j.yjmcc.2024.10.007
Stephan De Waard, Helene Hinnen, Jan P. Kucera
Reentry, the most common cause of severe arrhythmias, is initiated by slow conduction and conduction block. Hence, evaluating conduction velocity and conduction block is of primary importance. However, the assessment of cardiac conduction safety in experimental and clinical settings remains elusive. To identify markers of conduction instability that can be determined experimentally, we developed an approach based on new pacing paradigms. Conduction across a cardiac tissue expansion was assessed in computer simulations and in experiments using cultures of neonatal murine cardiomyocytes on microelectrode arrays. Simulated and in vitro tissues were paced at a progressively increasing rate, with stochastic or alternating variations of cycle length, until conduction block occurred. Increasing pacing rate led to conduction block near the expansion. When stochastic or alternating variations were introduced into the pacing protocol, the standard deviation and the amplitude of alternating variations of local conduction times emerged as markers of unstable conduction prone to block. In both simulations and experiments, conduction delays were prolonged at the expansion but increased only slightly during the pacing protocol. In contrast, these markers of instability increased several-fold, early before block occurrence. The first and second moments of these two metrics provided an estimation of the site of block and the accuracy of this estimation. Therefore, when beat-to-beat variations of pacing cycle length are introduced into a pacing protocol, the local variability of conduction permits to predict sites of block. Our pacing paradigms may have translational applications in clinical cardiac electrophysiology, particularly in identifying ablation targets during mapping procedures.
再通是导致严重心律失常的最常见原因,由缓慢传导和传导阻滞引起。因此,评估传导速度和传导阻滞至关重要。然而,在实验和临床环境中对心脏传导安全性的评估仍然难以捉摸。为了找出可通过实验确定的传导不稳定性标志物,我们开发了一种基于新起搏范式的方法。在计算机模拟和使用微电极阵列上的新生小鼠心肌细胞培养实验中,我们评估了心脏组织扩张时的传导情况。模拟和体外组织的起搏频率逐渐增加,周期长度随机或交替变化,直至发生传导阻滞。起搏频率的增加会导致扩张附近的传导阻滞。在起搏方案中引入随机或交替变化时,局部传导时间交替变化的标准偏差和振幅成为容易发生传导阻滞的不稳定传导的标志。在模拟和实验中,传导延迟在扩容时延长,但在起搏方案中仅轻微增加。与此相反,这些不稳定的标志物在阻滞发生前的早期增加了数倍。这两个指标的第一矩和第二矩提供了对阻滞部位的估计以及这种估计的准确性。因此,在起搏方案中引入起搏周期长度的逐次变化时,传导的局部变化可预测阻滞部位。我们的起搏范式可能会在临床心脏电生理学中得到转化应用,尤其是在制图过程中确定消融目标方面。
{"title":"Stochastic and alternating pacing paradigms to assess the stability of cardiac conduction","authors":"Stephan De Waard,&nbsp;Helene Hinnen,&nbsp;Jan P. Kucera","doi":"10.1016/j.yjmcc.2024.10.007","DOIUrl":"10.1016/j.yjmcc.2024.10.007","url":null,"abstract":"<div><div>Reentry, the most common cause of severe arrhythmias, is initiated by slow conduction and conduction block. Hence, evaluating conduction velocity and conduction block is of primary importance. However, the assessment of cardiac conduction safety in experimental and clinical settings remains elusive. To identify markers of conduction instability that can be determined experimentally, we developed an approach based on new pacing paradigms. Conduction across a cardiac tissue expansion was assessed in computer simulations and in experiments using cultures of neonatal murine cardiomyocytes on microelectrode arrays. Simulated and in vitro tissues were paced at a progressively increasing rate, with stochastic or alternating variations of cycle length, until conduction block occurred. Increasing pacing rate led to conduction block near the expansion. When stochastic or alternating variations were introduced into the pacing protocol, the standard deviation and the amplitude of alternating variations of local conduction times emerged as markers of unstable conduction prone to block. In both simulations and experiments, conduction delays were prolonged at the expansion but increased only slightly during the pacing protocol. In contrast, these markers of instability increased several-fold, early before block occurrence. The first and second moments of these two metrics provided an estimation of the site of block and the accuracy of this estimation. Therefore, when beat-to-beat variations of pacing cycle length are introduced into a pacing protocol, the local variability of conduction permits to predict sites of block. Our pacing paradigms may have translational applications in clinical cardiac electrophysiology, particularly in identifying ablation targets during mapping procedures.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 20-33"},"PeriodicalIF":4.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Another-regulin regulates cardiomyocyte calcium handling via integration of neuroendocrine signaling with SERCA2a activity 另一种胰岛素通过整合神经内分泌信号和 SERCA2a 活性来调节心肌细胞的钙处理。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-20 DOI: 10.1016/j.yjmcc.2024.10.008
Keira R. Hassel , Aaron M. Gibson , Jaroslava Šeflová , Ellen E. Cho , N. Scott Blair , Catherine D. Van Raamsdonk , Douglas M. Anderson , Seth L. Robia , Catherine A. Makarewich
Calcium (Ca2+) dysregulation is a hallmark feature of cardiovascular disease. Intracellular Ca2+ regulation is essential for proper heart function and is controlled by the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a). Another-regulin (ALN) is a newly discovered cardiomyocyte-expressed SERCA2a inhibitor, suggesting cardiomyocyte Ca2+-handling is more complex than previously appreciated. To study the role of ALN in cardiomyocytes, we generated ALN null mice (knockout, KO) and found that cardiomyocytes from these animals displayed enhanced Ca2+ cycling and contractility compared to wildtype (WT) mice, indicating enhanced SERCA2a activity. In vitro and in vivo studies show that ALN is post-translationally modified via phosphorylation on Serine 19 (S19), suggesting this contributes to its ability to regulate SERCA2a. Immunoprecipitation and FRET analysis of ALN-WT, phospho-deficient ALN (S19A), or phosphomimetic ALN (S19D) revealed that S19 phosphorylation alters the SERCA2a-ALN interaction, leading to relief of its inhibitory effects. Adeno-associated virus mediated delivery of ALN-WT or phospho-mutant ALN-S19A/D in ALN KO mice showed that cardiomyocyte-specific expression of phospho-deficient ALN-S19A resulted in increased SERCA2a inhibition characterized by reduced rates of cytoplasmic Ca2+ clearance compared to ALN-WT and ALN-S19D expressing cells, further supporting a role for this phosphorylation event in controlling SERCA2a-regulation by ALN. Levels of ALN phosphorylation were markedly increased in cardiomyocytes in response to Gαq agonists (angiotensin II, endothelin-1, phenylephrine) and Gαq-mediated phosphorylation of ALN translated to increased Ca2+ cycling in cardiomyocytes from WT but not ALN KO mice. Collectively, these results indicate that ALN uniquely regulates Ca2+ handling in cardiomyocytes via integration of neuroendocrine signaling with SERCA2a activity.
钙(Ca2+)失调是心血管疾病的一个标志性特征。细胞内 Ca2+ 的调节对心脏的正常功能至关重要,它由肌浆/内质网 Ca2+ ATPase(SERCA2a)控制。另一种调节蛋白(ALN)是一种新发现的心肌细胞表达的 SERCA2a 抑制剂,这表明心肌细胞的 Ca2+ 处理比以前认识到的更为复杂。为了研究 ALN 在心肌细胞中的作用,我们产生了 ALN 空断小鼠(基因敲除,KO),发现与野生型(WT)小鼠相比,这些动物的心肌细胞显示出增强的 Ca2+ 循环和收缩力,表明 SERCA2a 活性增强。体外和体内研究表明,ALN通过丝氨酸19(S19)上的磷酸化进行翻译后修饰,表明这有助于其调节SERCA2a的能力。对 ALN-WT、磷酸化缺陷 ALN(S19A)或磷酸拟态 ALN(S19D)的免疫沉淀和 FRET 分析表明,S19 磷酸化改变了 SERCA2a 与 ALN 的相互作用,导致其抑制作用减弱。腺相关病毒介导的 ALN-WT 或磷酸化突变 ALN-S19A/D 在 ALN KO 小鼠中的传递表明,与 ALN-WT 和 ALN-S19D 表达细胞相比,心肌细胞特异性表达磷酸化缺陷 ALN-S19A 会导致 SERCA2a 抑制作用增强,其特征是细胞质 Ca2+ 清除率降低,这进一步证明了这种磷酸化事件在 ALN 控制 SERCA2a 调节中的作用。在 Gαq 激动剂(血管紧张素 II、内皮素-1、苯肾上腺素)作用下,心肌细胞中的 ALN 磷酸化水平显著增加,Gαq 介导的 ALN 磷酸化在 WT 而非 ALN KO 小鼠的心肌细胞中转化为增加的 Ca2+ 循环。总之,这些结果表明,ALN 通过整合神经内分泌信号和 SERCA2a 活性,对心肌细胞中的 Ca2+ 处理进行独特的调节。
{"title":"Another-regulin regulates cardiomyocyte calcium handling via integration of neuroendocrine signaling with SERCA2a activity","authors":"Keira R. Hassel ,&nbsp;Aaron M. Gibson ,&nbsp;Jaroslava Šeflová ,&nbsp;Ellen E. Cho ,&nbsp;N. Scott Blair ,&nbsp;Catherine D. Van Raamsdonk ,&nbsp;Douglas M. Anderson ,&nbsp;Seth L. Robia ,&nbsp;Catherine A. Makarewich","doi":"10.1016/j.yjmcc.2024.10.008","DOIUrl":"10.1016/j.yjmcc.2024.10.008","url":null,"abstract":"<div><div>Calcium (Ca<sup>2+</sup>) dysregulation is a hallmark feature of cardiovascular disease. Intracellular Ca<sup>2+</sup> regulation is essential for proper heart function and is controlled by the sarco/endoplasmic reticulum Ca<sup>2+</sup> ATPase (SERCA2a). Another-regulin (ALN) is a newly discovered cardiomyocyte-expressed SERCA2a inhibitor, suggesting cardiomyocyte Ca<sup>2+</sup>-handling is more complex than previously appreciated. To study the role of ALN in cardiomyocytes, we generated ALN null mice (knockout, KO) and found that cardiomyocytes from these animals displayed enhanced Ca<sup>2+</sup> cycling and contractility compared to wildtype (WT) mice, indicating enhanced SERCA2a activity. In vitro and in vivo studies show that ALN is post-translationally modified via phosphorylation on Serine 19 (S19), suggesting this contributes to its ability to regulate SERCA2a. Immunoprecipitation and FRET analysis of ALN-WT, phospho-deficient ALN (S19A), or phosphomimetic ALN (S19D) revealed that S19 phosphorylation alters the SERCA2a-ALN interaction, leading to relief of its inhibitory effects. Adeno-associated virus mediated delivery of ALN-WT or phospho-mutant ALN-S19A/D in ALN KO mice showed that cardiomyocyte-specific expression of phospho-deficient ALN-S19A resulted in increased SERCA2a inhibition characterized by reduced rates of cytoplasmic Ca<sup>2+</sup> clearance compared to ALN-WT and ALN-S19D expressing cells, further supporting a role for this phosphorylation event in controlling SERCA2a-regulation by ALN. Levels of ALN phosphorylation were markedly increased in cardiomyocytes in response to Gα<sub>q</sub> agonists (angiotensin II, endothelin-1, phenylephrine) and Gα<sub>q</sub>-mediated phosphorylation of ALN translated to increased Ca<sup>2+</sup> cycling in cardiomyocytes from WT but not ALN KO mice. Collectively, these results indicate that ALN uniquely regulates Ca<sup>2+</sup> handling in cardiomyocytes via integration of neuroendocrine signaling with SERCA2a activity.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 45-58"},"PeriodicalIF":4.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Panorama of artery endothelial cell dysfunction in pulmonary arterial hypertension 肺动脉高压中动脉内皮细胞功能障碍的全景图。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-20 DOI: 10.1016/j.yjmcc.2024.10.004
Ying-Huizi Shen , Dong Ding , Tian-Yu Lian , Bao-Chen Qiu , Yi Yan , Pei-Wen Wang , Wei-Hua Zhang , Zhi-Cheng Jing
Pulmonary arterial hypertension (PAH) is a fatal lung disease characterized by progressive pulmonary vascular remodeling. The initial cause of pulmonary vascular remodeling is the dysfunction of pulmonary arterial endothelial cells (PAECs), manifested by changes in the categorization of cell subtypes, endothelial programmed cell death, such as apoptosis, necroptosis, pyroptosis, ferroptosis, et al., overproliferation, senescence, metabolic reprogramming, endothelial-to-mesenchymal transition, mechanosensitivity, and regulation ability of peripheral cells. Therefore, it is essential to explore the mechanism of endothelial dysfunction in the context of PAH. This review aims to provide a comprehensive understanding of the molecular mechanisms underlying endothelial dysfunction in PAH. We highlight the developmental process of PAECs and changes in PAH and summarise the latest classification of endothelial dysfunction. Our review could offer valuable insights into potential novel EC-specific targets for preventing and treating PAH.
肺动脉高压(PAH)是一种以进行性肺血管重塑为特征的致命性肺部疾病。肺血管重塑的最初原因是肺动脉内皮细胞(PAECs)功能障碍,表现为细胞亚型分类的变化、内皮细胞程序性死亡(如凋亡、坏死、热凋亡、铁凋亡等)、过度增殖、衰老、代谢重编程、内皮细胞向间质转化、机械敏感性和外周细胞的调节能力。因此,探索 PAH 背景下内皮功能障碍的机制至关重要。本综述旨在全面了解 PAH 内皮功能障碍的分子机制。我们强调了 PAECs 的发育过程和 PAH 中的变化,并总结了内皮功能障碍的最新分类。我们的综述可为预防和治疗 PAH 的潜在新型特异性 EC 靶点提供有价值的见解。
{"title":"Panorama of artery endothelial cell dysfunction in pulmonary arterial hypertension","authors":"Ying-Huizi Shen ,&nbsp;Dong Ding ,&nbsp;Tian-Yu Lian ,&nbsp;Bao-Chen Qiu ,&nbsp;Yi Yan ,&nbsp;Pei-Wen Wang ,&nbsp;Wei-Hua Zhang ,&nbsp;Zhi-Cheng Jing","doi":"10.1016/j.yjmcc.2024.10.004","DOIUrl":"10.1016/j.yjmcc.2024.10.004","url":null,"abstract":"<div><div>Pulmonary arterial hypertension (PAH) is a fatal lung disease characterized by progressive pulmonary vascular remodeling. The initial cause of pulmonary vascular remodeling is the dysfunction of pulmonary arterial endothelial cells (PAECs), manifested by changes in the categorization of cell subtypes, endothelial programmed cell death, such as apoptosis, necroptosis, pyroptosis, ferroptosis, et al., overproliferation, senescence, metabolic reprogramming, endothelial-to-mesenchymal transition, mechanosensitivity, and regulation ability of peripheral cells. Therefore, it is essential to explore the mechanism of endothelial dysfunction in the context of PAH. This review aims to provide a comprehensive understanding of the molecular mechanisms underlying endothelial dysfunction in PAH. We highlight the developmental process of PAECs and changes in PAH and summarise the latest classification of endothelial dysfunction. Our review could offer valuable insights into potential novel EC-specific targets for preventing and treating PAH.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 61-77"},"PeriodicalIF":4.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiomyocyte myofilament function in common animal models of heart failure with preserved ejection fraction 射血分数保留型心力衰竭常见动物模型的心肌细胞肌丝功能。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-18 DOI: 10.1016/j.yjmcc.2024.10.005
Vivek P. Jani , Navid Koleini , Axel J. Fenwick , Thomas E. Sharp , Traci T. Goodchild , Joseph A. Hill , David J. Lefer , Anthony Cammarato , David A. Kass
Human cardiomyocytes from very obese patients with heart failure and preserved ejection fraction (HFpEF) have markedly depressed calcium-activated tension and increased resting stiffness. To test if either are recapitulated by obese-HFpEF animal models, tension‑calcium and tension-sarcomere length relations were measured in myocytes from mice on a high fat diet (HFD) with L-NAME, ZSF1 rats, and Göttingen minipigs on HFD + DOCA (MP). Only MP myocytes displayed reduced Ca2+-activated tension, and none exhibited increased resting stiffness versus respective controls. Consistent with prior myofibrillar data, crossbridge attachment and detachment rates at matched tension were slower in rodent models, and detachment slower in MP.
患有心力衰竭和射血分数保留(HFpEF)的极度肥胖患者的人类心肌细胞具有明显的钙激活张力降低和静息僵硬度增加的特点。为了测试肥胖-HFpEF 动物模型是否再现了这两种情况,我们测量了高脂饮食(HFD)加 L-NAME、ZSF1 大鼠和高脂饮食 + DOCA(MP)的哥廷根小型猪心肌细胞的张力-钙和张力-肌丝长度关系。与各自的对照组相比,只有 MP 心肌细胞显示出 Ca2+ 激活张力降低,而静息僵硬度均未增加。与之前的肌纤维数据一致,在啮齿类动物模型中,匹配张力下的交桥附着和脱落速度较慢,而在 MP 中,脱落速度较慢。
{"title":"Cardiomyocyte myofilament function in common animal models of heart failure with preserved ejection fraction","authors":"Vivek P. Jani ,&nbsp;Navid Koleini ,&nbsp;Axel J. Fenwick ,&nbsp;Thomas E. Sharp ,&nbsp;Traci T. Goodchild ,&nbsp;Joseph A. Hill ,&nbsp;David J. Lefer ,&nbsp;Anthony Cammarato ,&nbsp;David A. Kass","doi":"10.1016/j.yjmcc.2024.10.005","DOIUrl":"10.1016/j.yjmcc.2024.10.005","url":null,"abstract":"<div><div>Human cardiomyocytes from very obese patients with heart failure and preserved ejection fraction (HFpEF) have markedly depressed calcium-activated tension and increased resting stiffness. To test if either are recapitulated by obese-HFpEF animal models, tension‑calcium and tension-sarcomere length relations were measured in myocytes from mice on a high fat diet (HFD) with L-NAME, ZSF1 rats, and Göttingen minipigs on HFD + DOCA (MP). Only MP myocytes displayed reduced Ca<sup>2+</sup>-activated tension, and none exhibited increased resting stiffness versus respective controls. Consistent with prior myofibrillar data, crossbridge attachment and detachment rates at matched tension were slower in rodent models, and detachment slower in MP.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 34-39"},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alda-1 attenuation of binge alcohol-caused atrial arrhythmias through a novel mechanism of suppressed c-Jun N-terminal Kinase-2 activity Alda-1 通过抑制 c-Jun N-terminal Kinase-2 活性的新机制,减轻酗酒导致的房性心律失常
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-11 DOI: 10.1016/j.yjmcc.2024.10.003
Jiajie Yan , Saugat Khanal , Yuanyuan Cao , Nikola Ricchiuti , Alma Nani , S.R. Wayne Chen , Michael Fill , Dan J. Bare , Xun Ai
Holiday Heart Syndrome (HHS) is caused by excessive binge alcohol consumption, and atrial fibrillation (AF) is the most common arrhythmia among HHS patients. AF is associated with substantial morbidity and mortality, making its prevention and treatment of high clinical interest. This study defines the anti-AF action of Alda-1 (an established cardioprotective agent) and the underlying mechanisms of the action in our well-characterized HHS and cellular models. We found that Alda-1 effectively eliminated binge alcohol-evoked Ca2+ triggered activities (Ca2+ waves, prolonged Ca2+ transient diastolic decay) and arrhythmia inducibility in intact mouse atria. We then demonstrated that alcohol impaired human RyR2 channels (isolated from organ donors' hearts). The functional role of alcohol-caused RyR2 channel dysfunction in Ca2+ triggered arrhythmic activities was evidenced in a unique transgenic mouse model with a loss-of-function mutation (RyR2E4872Q+/−). Alda-1 is known to activate aldehyde dehydrogenase 2 (ALDH2), a key enzyme in alcohol detoxification. However, we found an increased level of ALDH2 and a preserved normal balance of pro- vs anti-apoptotic signaling in binge alcohol exposed hearts and H9c2 differentiated myocytes, which suggests that the link of alcohol-ALDH2-apoptosis is unlikely to be a key factor leading to binge alcohol-evoked arrhythmogenicity. We have previously reported that binge alcohol-activated stress response kinase JNK2 causatively drives Ca2+-triggered atrial arrhythmogenicity. Here, we found that JNK2-specific inhibition in either isolated human RyR2 channels or intact mouse atria abolished alcohol-evoked RyR2 channel dysfunction and Ca2+ triggered arrhythmic activities, suggesting a strong alcohol-JNK2-RyR2 interaction in atrial arrhythmogenicity. Furthermore, we revealed, for the first time, that Alda-1 suppresses JNK2 (but not JNK1) enzyme activity independently of ALDH2, which in turn alleviates binge alcohol-evoked Ca2+ triggered atrial arrhythmogenesis. Our findings provide novel mechanistic insights into the anti-arrhythmic action of Alda-1 and suggest that Alda-1 represents a potential preventative agent for AF management for HHS patients.
假日心脏综合征(HHS)是由过度酗酒引起的,而心房颤动(AF)是假日心脏综合征患者中最常见的心律失常。房颤与严重的发病率和死亡率相关,因此其预防和治疗在临床上备受关注。本研究确定了 Alda-1(一种成熟的心脏保护剂)的抗房颤作用,以及在我们表征良好的高血压和细胞模型中的基本作用机制。我们发现,Alda-1 能有效消除暴饮暴食酒精诱发的 Ca2+ 触发活动(Ca2+ 波、延长的 Ca2+ 瞬时舒张衰减)以及完整小鼠心房的心律失常诱导性。然后,我们证明酒精会损害人类 RyR2 通道(从器官捐献者的心脏中分离)。酒精导致的 RyR2 通道功能障碍在 Ca2+ 触发的心律失常活动中的功能作用在一个独特的功能缺失突变(RyR2E4872Q+/-)转基因小鼠模型中得到了证实。众所周知,Alda-1 能激活醛脱氢酶 2(ALDH2),这是酒精解毒过程中的一种关键酶。然而,我们发现在暴饮暴食酒精暴露的心脏和 H9c2 分化的心肌细胞中,ALDH2 的水平升高,而促凋亡与抗凋亡信号的平衡保持正常,这表明酒精-ALDH2-凋亡之间的联系不太可能是导致暴饮暴食酒精诱发心律失常的关键因素。我们以前曾报道过,暴饮暴食酒精激活的应激反应激酶 JNK2 是 Ca2+ 触发心房致心律失常的诱因。在这里,我们发现在离体的人类 RyR2 通道或完整的小鼠心房中抑制 JNK2 特异性可消除酒精诱发的 RyR2 通道功能障碍和 Ca2+ 触发的心律失常活动,这表明酒精-JNK2-RyR2 在心房致心律失常中具有很强的相互作用。此外,我们首次发现 Alda-1 可独立于 ALDH2 而抑制 JNK2(而非 JNK1)酶的活性,这反过来又减轻了酗酒诱发的 Ca2+ 触发的心房致心律失常。我们的研究结果为 Alda-1 的抗心律失常作用提供了新的机理认识,并表明 Alda-1 是一种潜在的预防性药物,可用于 HHS 患者的房颤治疗。
{"title":"Alda-1 attenuation of binge alcohol-caused atrial arrhythmias through a novel mechanism of suppressed c-Jun N-terminal Kinase-2 activity","authors":"Jiajie Yan ,&nbsp;Saugat Khanal ,&nbsp;Yuanyuan Cao ,&nbsp;Nikola Ricchiuti ,&nbsp;Alma Nani ,&nbsp;S.R. Wayne Chen ,&nbsp;Michael Fill ,&nbsp;Dan J. Bare ,&nbsp;Xun Ai","doi":"10.1016/j.yjmcc.2024.10.003","DOIUrl":"10.1016/j.yjmcc.2024.10.003","url":null,"abstract":"<div><div>Holiday Heart Syndrome (HHS) is caused by excessive binge alcohol consumption, and atrial fibrillation (AF) is the most common arrhythmia among HHS patients. AF is associated with substantial morbidity and mortality, making its prevention and treatment of high clinical interest. This study defines the anti-AF action of Alda-1 (an established cardioprotective agent) and the underlying mechanisms of the action in our well-characterized HHS and cellular models. We found that Alda-1 effectively eliminated binge alcohol-evoked Ca<sup>2+</sup> triggered activities (Ca<sup>2+</sup> waves, prolonged Ca<sup>2+</sup> transient diastolic decay) and arrhythmia inducibility in intact mouse atria. We then demonstrated that alcohol impaired human RyR2 channels (isolated from organ donors' hearts). The functional role of alcohol-caused RyR2 channel dysfunction in Ca<sup>2+</sup> triggered arrhythmic activities was evidenced in a unique transgenic mouse model with a loss-of-function mutation (RyR2<sup>E4872Q+/−</sup>). Alda-1 is known to activate aldehyde dehydrogenase 2 (ALDH2), a key enzyme in alcohol detoxification. However, we found an increased level of ALDH2 and a preserved normal balance of pro- <em>vs</em> anti-apoptotic signaling in binge alcohol exposed hearts and H9c2 differentiated myocytes, which suggests that the link of alcohol-ALDH2-apoptosis is unlikely to be a key factor leading to binge alcohol-evoked arrhythmogenicity. We have previously reported that binge alcohol-activated stress response kinase JNK2 causatively drives Ca<sup>2+</sup>-triggered atrial arrhythmogenicity. Here, we found that JNK2-specific inhibition in either isolated human RyR2 channels or intact mouse atria abolished alcohol-evoked RyR2 channel dysfunction and Ca<sup>2+</sup> triggered arrhythmic activities, suggesting a strong alcohol-JNK2-RyR2 interaction in atrial arrhythmogenicity. Furthermore, we revealed, for the first time, that Alda-1 suppresses JNK2 (but not JNK1) enzyme activity independently of ALDH2, which in turn alleviates binge alcohol-evoked Ca<sup>2+</sup> triggered atrial arrhythmogenesis. Our findings provide novel mechanistic insights into the anti-arrhythmic action of Alda-1 and suggest that Alda-1 represents a potential preventative agent for AF management for HHS patients.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 11-19"},"PeriodicalIF":4.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human embryonic stem cell-derived cardiovascular progenitor cells stimulate cardiomyocyte cell cycle activity via activating the PI3K/Akt pathway 人类胚胎干细胞衍生的心血管祖细胞通过激活 PI3K/Akt 通路刺激心肌细胞的细胞周期活动。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-10 DOI: 10.1016/j.yjmcc.2024.10.002
Zhongyan Chen , Xiujian Yu , Minxia Ke , Hao Li , Yun Jiang , Peng Zhang , Jiliang Tan , Nan Cao , Huang-Tian Yang
Promoting endogenous cardiomyocyte proliferation is crucial for repairing infarcted hearts. Implantation of human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) promotes healing of infarcted hearts. However, little is known regarding their impact on host cardiomyocyte proliferation. Here, we revealed that hCVPC implantation into mouse infarcted hearts induced dedifferentiation and cell cycle re-entry of host cardiomyocytes, which was further confirmed in vitro by hCVPC-conditioned medium. Mechanistically, the PI3K/Akt signaling pathway mediated hCVPC-induced cardiomyocyte cell cycle re-entry. The findings reveal the novel function of hCVPCs in triggering cardiomyocyte dedifferentiation and cell cycle activation and highlight a strategy utilizing cells at early developmental stages to rejuvenate adult cardiomyocytes.
促进内源性心肌细胞增殖是修复梗死心脏的关键。植入人多能干细胞衍生的心血管祖细胞(hCVPCs)可促进梗死心脏的愈合。然而,人们对其对宿主心肌细胞增殖的影响知之甚少。在这里,我们发现将 hCVPC 植入小鼠梗死心脏可诱导宿主心肌细胞发生去分化和细胞周期再入,hCVPC 调节培养基在体外进一步证实了这一点。从机制上讲,PI3K/Akt 信号通路介导了 hCVPC 诱导的心肌细胞细胞周期重入。这些发现揭示了 hCVPC 在引发心肌细胞去分化和细胞周期活化方面的新功能,并强调了一种利用处于早期发育阶段的细胞使成年心肌细胞恢复活力的策略。
{"title":"Human embryonic stem cell-derived cardiovascular progenitor cells stimulate cardiomyocyte cell cycle activity via activating the PI3K/Akt pathway","authors":"Zhongyan Chen ,&nbsp;Xiujian Yu ,&nbsp;Minxia Ke ,&nbsp;Hao Li ,&nbsp;Yun Jiang ,&nbsp;Peng Zhang ,&nbsp;Jiliang Tan ,&nbsp;Nan Cao ,&nbsp;Huang-Tian Yang","doi":"10.1016/j.yjmcc.2024.10.002","DOIUrl":"10.1016/j.yjmcc.2024.10.002","url":null,"abstract":"<div><div>Promoting endogenous cardiomyocyte proliferation is crucial for repairing infarcted hearts. Implantation of human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) promotes healing of infarcted hearts. However, little is known regarding their impact on host cardiomyocyte proliferation. Here, we revealed that hCVPC implantation into mouse infarcted hearts induced dedifferentiation and cell cycle re-entry of host cardiomyocytes, which was further confirmed in vitro by hCVPC-conditioned medium. Mechanistically, the PI3K/Akt signaling pathway mediated hCVPC-induced cardiomyocyte cell cycle re-entry. The findings reveal the novel function of hCVPCs in triggering cardiomyocyte dedifferentiation and cell cycle activation and highlight a strategy utilizing cells at early developmental stages to rejuvenate adult cardiomyocytes.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 5-10"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessing and interpreting diastolic function in animal models of heart disease 评估和解释心脏病动物模型的舒张功能。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-04 DOI: 10.1016/j.yjmcc.2024.10.001
David A. Kass
Increasing interest in identifying the causes of and treatments for heart failure with preserved ejection fraction and cardiac fibrosis has spawned a focus on measures of cardiac diastolic function. The methods, their underlying principals and mechanics, and caveats to their measurement were largely worked out decades ago, but some of this seems a bit forgotten as scientists working in the field now have backgrounds more in molecular and cellular biology. This perspective was spawned by seeing the growing number of studies where diastolic function analysis is a key parameter used to justify a given pre-clinical model or to show the consequences of a particular genetic or pharmacological therapy. The goals are to discuss what comprises and influences diastolic function, how it is measured, what the parameters mean and what their limitations are, and what comprises evidence for pathophysiologically meaningful diastolic dysfunction.
人们对确定射血分数保留型心力衰竭和心脏纤维化的原因和治疗方法越来越感兴趣,这促使人们开始关注心脏舒张功能的测量方法。这些方法、其基本原理和力学以及测量时的注意事项在几十年前就已基本确定,但由于现在从事该领域工作的科学家更多具有分子和细胞生物学背景,其中一些似乎已被遗忘。在越来越多的研究中,舒张功能分析是一个关键参数,用来证明特定临床前模型的合理性,或显示特定遗传或药物疗法的后果。其目的是讨论舒张功能的组成和影响因素、测量方法、参数的含义及其局限性,以及具有病理生理学意义的舒张功能障碍的证据组成。
{"title":"Assessing and interpreting diastolic function in animal models of heart disease","authors":"David A. Kass","doi":"10.1016/j.yjmcc.2024.10.001","DOIUrl":"10.1016/j.yjmcc.2024.10.001","url":null,"abstract":"<div><div>Increasing interest in identifying the causes of and treatments for heart failure with preserved ejection fraction and cardiac fibrosis has spawned a focus on measures of cardiac diastolic function. The methods, their underlying principals and mechanics, and caveats to their measurement were largely worked out decades ago, but some of this seems a bit forgotten as scientists working in the field now have backgrounds more in molecular and cellular biology. This perspective was spawned by seeing the growing number of studies where diastolic function analysis is a key parameter used to justify a given pre-clinical model or to show the consequences of a particular genetic or pharmacological therapy. The goals are to discuss what comprises and influences diastolic function, how it is measured, what the parameters mean and what their limitations are, and what comprises evidence for pathophysiologically meaningful diastolic dysfunction.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 1-4"},"PeriodicalIF":4.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of molecular and cellular cardiology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1