Journal of molecular and cellular cardiology最新文献

英文中文

Corrigendum to “Human embryonic stem cell-derived cardiovascular progenitor cells stimulate cardiomyocyte cell cycle activity via activating the PI3K/Akt pathway” [J. Mol. Cell. Cardiol. 197 (2024) 5–10.] 人类胚胎干细胞衍生的心血管祖细胞通过激活PI3K/Akt通路刺激心肌细胞周期活性[J]。摩尔。细胞。心脏杂志。197(2024)5-10。

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-09-09 DOI: 10.1016/j.yjmcc.2025.08.011

Zhongyan Chen , Xiujian Yu , Minxia Ke , Hao Li , Yun Jiang , Peng Zhang , Jiliang Tan , Nan Cao , Huang-Tian Yang

引用次数: 0

Klotho attenuates D-galactose-induced cardiac aging through the ROS/NLRP3/pyroptosis pathway Klotho通过ROS/NLRP3/焦亡途径减缓d -半乳糖诱导的心脏衰老。

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-09-08 DOI: 10.1016/j.yjmcc.2025.09.004

Sui-sui Wang , Xu Zhang , Ze-zhi Ke , Yu-xin Zeng , Xiu-yun Wen , Wen-bin Liu , Jie Zhao , Xiao-dong Zhuang , Li-zhen Liao

Objective

Activation of NLRP3 inflammasome contributes to cardiac aging progression. Klotho, a recognised anti-aging protein, exerts protective effects against cardiac aging. In this study, we aimed to elucidate the protective effects of Klotho on D-galactose (D-gal)-induced cardiac aging and the underlying mechanisms.

Methods

Aging severity in mice was evaluated based on coat condition and serum Klotho levels. Serum levels of interleukin (IL)-1β, lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde were measured to assess cardiac oxidative stress and inflammatory response damage. Cardiac function was evaluated using echocardiography, whereas heart histopathological changes were observed through haematoxylin-eosin (HE) staining, Masson staining, and heart index. Cardiac aging was further assessed with β-galactosidase staining and western blot analysis of aging-related proteins (P53 and P21). Pyroptosis-related protein expression was assessed via western blot, and cardiac tissue reactive oxygen species (ROS) expression levels were determined through dihydroethidium staining. Similar analyses were conducted on D-gal-treated H9C2 cardiomyocytes.

Results

Compared to wild-type aged mice, Klotho-treated and NLRP3 knockout mice showed markedly reduced back hair loss, elevated serum Klotho and SOD levels, reduced serum IL-1β and LDH, enhanced left ventricular ejection fraction, left ventricular fractional shortening, peak E to peak A ratio, diminished heart size, cardiomyocyte hypertrophy and collagen deposition. Decreased cardiac aging markers, apoptosis-associated speck-like protein (ASC) formation, NLRP3 expression, cleaved-caspase-1, gasdermin D (GSDMD), IL-1β, and IL-18, and lower ROS levels were observed in cardiac tissues. These protective effects were abolished upon Nigericin injection.

Conclusions

Klotho delays D-gal-induced cardiac aging by regulating the ROS/NLRP3/pyroptosis pathway.

目的：NLRP3炎性体的激活与心脏衰老进程有关。Klotho是一种公认的抗衰老蛋白，对心脏衰老具有保护作用。在本研究中，我们旨在阐明Klotho对d -半乳糖（D-gal）诱导的心脏衰老的保护作用及其机制。方法：以被毛状况和血清Klotho水平评价小鼠衰老严重程度。测定血清白细胞介素(IL)-1β、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）和丙二醛水平，以评估心脏氧化应激和炎症反应损伤。采用超声心动图评价心脏功能，通过血红素-伊红（HE）染色、Masson染色和心脏指数观察心脏组织病理变化。通过β-半乳糖苷酶染色和衰老相关蛋白（P53和P21）的western blot分析进一步评估心脏衰老。western blot检测焦热相关蛋白表达，双氢乙啶染色检测心脏组织活性氧（ROS）表达水平。对d -gal处理的H9C2心肌细胞进行了类似的分析。结果：与野生型老年小鼠相比，Klotho处理和NLRP3基因敲除小鼠的背部脱发明显减少，血清Klotho和SOD水平升高，血清IL-1β和LDH降低，左心室射血分数增加，左心室分数缩短，E峰与A峰比值增加，心脏大小减小，心肌细胞肥大，胶原沉积明显减少。心脏老化标志物、凋亡相关斑点样蛋白（ASC）形成、NLRP3表达、裂解caspase-1、气皮蛋白D （GSDMD）、IL-1β和IL-18降低，心脏组织中ROS水平降低。注射尼日利亚菌素后，这些保护作用消失。结论：Klotho通过调节ROS/NLRP3/焦亡通路延缓d -gal诱导的心脏衰老。

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引用次数: 0

Flow cytometry of the myocardium: An end-to-end analysis of adult cardiomyocytes isolated from pig and mouse hearts 心肌的流式细胞术：从猪和小鼠心脏分离的成人心肌细胞的端到端分析。

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-09-04 DOI: 10.1016/j.yjmcc.2025.09.003

Alex Gallinat, Xisheng Li, Nikhil P. Raisinghani, Sabrina La Salvia, Anh Phan, Shihong Zhang, Spyros A. Mavropoulos, Samta Veera, Seonghun Yoon, Kiyotake Ishikawa, Susmita Sahoo

Selective therapeutic targeting of cardiomyocytes (CMs) and non-myocytes (NMs) within the heart is an active field of research. The success of those novel therapeutic strategies is linked to the ability to accurately assess uptake and gene delivery efficiencies in clinically relevant animal models. Nevertheless, quantification at the single cell level remains a significant challenge. While flow cytometry offers the possibility of an accurate and direct single-cell quantification, the unique structural and physical properties of CMs complicate the analysis. There are no standardized methods reported for the flow cytometry analysis of adult CMs, which is a significant pitfall in the field. Here, we address this gap and introduce a robust and optimized method for the successful flow cytometry analysis of isolated CMs. Starting from tissue digestion, we present a simple workflow for the isolation and characterization of CMs and NMs, tested and validated for pig and mouse. We demonstrate the versatility of this method through three biologically relevant applications. First, we introduce a model to quantify CMs nucleation based on DNA content distribution. Second, we assess cell-specific in vivo gene delivery with AAV-Luc in pig hearts. And last, we demonstrate how structural remodeling of CMs affects their light scattering properties, in a pressure overload-induced hypertrophy mouse model. Together, these findings establish a flexible and quantitative platform for single-cell analysis of cardiac cell populations in both basic and translational cardiovascular research.

心脏内心肌细胞（CMs）和非肌细胞（NMs）的选择性靶向治疗是一个活跃的研究领域。这些新型治疗策略的成功与在临床相关动物模型中准确评估摄取和基因传递效率的能力有关。然而，单细胞水平的定量仍然是一个重大挑战。虽然流式细胞术提供了准确和直接的单细胞定量的可能性，但CMs独特的结构和物理性质使分析复杂化。成人CMs的流式细胞术分析还没有标准化的方法，这是该领域的一个重大缺陷。在这里，我们解决了这一差距，并引入了一种强大的优化方法，用于成功地对分离的CMs进行流式细胞术分析。从组织消化开始，我们提出了一种简单的分离和表征CMs和NMs的工作流程，并在猪和小鼠中进行了测试和验证。我们通过三个生物学相关的应用证明了这种方法的多功能性。首先，我们引入了一个基于DNA含量分布的CMs成核量化模型。其次，我们评估了AAV-Luc在猪心脏中的细胞特异性体内基因传递。最后，我们在压力过载诱导的肥厚小鼠模型中展示了CMs的结构重塑如何影响它们的光散射特性。总之，这些发现为基础和转化心血管研究中的心脏细胞群单细胞分析建立了一个灵活的定量平台。

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引用次数: 0

Circadian transcriptional repressors REV-ERBα/β and E4BP4 regulate cardiac function 昼夜节律转录抑制因子rev - erba /β和E4BP4调节心功能。

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-09-02 DOI: 10.1016/j.yjmcc.2025.09.001

Yilian Wang , Pieterjan Dierickx

Circadian rhythms are an endogenous timekeeping system with a period of approximately 24 h that regulate many aspects of body physiology to maintain organismal health. Dysregulation of circadian rhythmicity has been implicated in various human diseases such as cancer as well as metabolic and cardiovascular disorders. Intrinsic, biological oscillations are regulated by the circadian clock, a molecular transcriptional/translational feedback loop that involves activators such as BMAL1 and CLOCK, and repressors such as REV-ERBα/β and E4BP4. Recent studies have shown that REV-ERBs and E4BP4 play a key role in regulating cardiac gene expression programs and metabolism. Here, we discuss these findings and highlight the mechanisms of their role in healthy and diseased hearts. Since REV-ERBs are drug targets, they hold potential for the treatment of cardiovascular disorders that are linked to circadian dysregulation or metabolic imbalance.

昼夜节律是一种内源性计时系统，其周期约为24 h，调节身体生理的许多方面以维持机体健康。昼夜节律失调与各种人类疾病，如癌症以及代谢和心血管疾病有关。内在的生物振荡是由生物钟调节的，生物钟是一个分子转录/翻译反馈回路，包括激活因子如BMAL1和clock，以及抑制因子如rev - erba /β和E4BP4。最近的研究表明，REV-ERBs和E4BP4在调节心脏基因表达程序和代谢中起关键作用。在这里，我们讨论这些发现，并强调其在健康和患病心脏中的作用机制。由于REV-ERBs是药物靶点，因此它们具有治疗与昼夜节律失调或代谢不平衡相关的心血管疾病的潜力。

引用次数: 0

Regulation of atrial and ventricular cardiomyocyte identity 心房和心室心肌细胞同一性的调节

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-08-26 DOI: 10.1016/j.yjmcc.2025.08.010

Shuliang Guo , Yingwei Liu , Angela Ryan , Ana Laura Lopez Serrano , Isabelle Deschenes , Jihyun Jang , Deqiang Li

Establishment and maintenance of specialized CMs in the heart is critical for the proper cardiac structure and function. Conversely, loss or gain of their identities is associated with various heart diseases such as cardiac arrythmia and cardiomyopathy. CM identity is established during early heart development and continues to be maintained under normal physiological condition, and this is predominantly accomplished by gene regulation. Our understanding of potential genetic, epigenetic or posttranscriptional programs that regulate CM identity (e.g., atrial or ventricular CM identity) is still quite limited. To this end, we summarize current understandings on atrial and ventricular CM identity regulations and discuss potential future research directions to unveil the underlying regulatory mechanisms.

在心脏中建立和维持专门的CMs对心脏的正常结构和功能至关重要。相反，他们身份的丧失或获得与各种心脏疾病，如心律失常和心肌病有关。CM身份是在心脏发育早期建立的，并在正常生理条件下继续维持，这主要是通过基因调控来完成的。我们对调节CM身份（例如心房或心室CM身份）的潜在遗传、表观遗传或转录后程序的理解仍然相当有限。为此，我们总结了目前对心房和心室CM同一性调节的认识，并讨论了潜在的未来研究方向，以揭示潜在的调节机制。

引用次数: 0

A simple approach of nuclei isolation for single nucleus multiome sequencing 单核多组测序中一种简单的核分离方法

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-08-21 DOI: 10.1016/j.yjmcc.2025.08.009

Yin Wang , Di Ren , Randy Kang , Kai Zhang , Yunqian Peng , Heather Zhou , Geming Lu , Junjie Guo , Adolfo Garcia-Ocaña , Yingfeng Deng , June-Wha Rhee , Zhao V. Wang

The emergence of single nucleus multiome sequencing (snMultiome-seq) technology has greatly advanced our understanding of various biological processes. However, existing experimental protocols fail to isolate high-quality nuclei from cryopreserved fibrous tissues, such as the heart, leading to low-quality downstream sequencing data. Here, we develop a simple and inexpensive approach for nuclei isolation from frozen tissues, named douncer-filter-gradient-centrifugation (DFGC). This protocol takes approximately 1.5 h to complete, including mincing (1 min), douncing (3 min), filtration (20 min), and density gradient centrifugation (40 min). To evaluate the effectiveness of the DFGC approach, we compare it with two commonly used methods for nuclei isolation – micro-beads and fluorescence-activated cell sorting (FACS). We demonstrate that the DFGC method performs in a preferred manner for the generation of both single nucleus gene expression and chromatin transposase accessibility data. We anticipate the DFGC method to be a mainstream approach for high-quality nuclei isolation in snMultiome-seq.

单核多组测序（snMultiome-seq）技术的出现极大地促进了我们对各种生物过程的理解。然而，现有的实验方案无法从冷冻保存的纤维组织（如心脏）中分离出高质量的细胞核，导致下游测序数据质量低。在这里，我们开发了一种简单而廉价的方法从冷冻组织中分离细胞核，称为下滤-梯度离心（DFGC）。该方案大约需要1.5小时完成，包括切碎（1分钟），浇注（3分钟），过滤（20分钟）和密度梯度离心（40分钟）。为了评估DFGC方法的有效性，我们将其与两种常用的细胞核分离方法-微珠和荧光活化细胞分选（FACS）进行了比较。我们证明了DFGC方法在生成单核基因表达和染色质转座酶可及性数据方面都是首选的方法。我们预计DFGC方法将成为snMultiome-seq中高质量核分离的主流方法。

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引用次数: 0

Cytoplasmic RBM20 gain-of-function induces atrial arrhythmogenicity independent of splicing defects in a novel murine model 在一种新的小鼠模型中，细胞质RBM20功能获得诱导心房心律失常不依赖于剪接缺陷

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-08-20 DOI: 10.1016/j.yjmcc.2025.08.007

Brijesh Sathian, Javed Iqbal, Syed Muhammad Ali

引用次数: 0

Corrigendum to “MMP19 in vascular smooth muscle cells protects against thoracic aortic aneurysm and dissection via the MMP19/Aggrecan/Wnt/β-catenin axis”[J Mol Cell Cardiol. 202 (2025) 35–49] “血管平滑肌细胞MMP19/Aggrecan/Wnt/β-catenin轴对胸主动脉瘤和夹层的保护作用”[J].中华检验医学杂志，2002(2):35-49。

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-08-20 DOI: 10.1016/j.yjmcc.2025.08.002

Baihui Ma , Qingyi Zeng , Fangfang Yang , Hang Yang , Wenke Li , Rei Fu , Zeyu Cai , Guoyan Zhu , Mingyao Luo , Zhou Zhou

引用次数: 0

Response to: Cytoplasmic RBM20 gain-of-function induces atrial arrhythmogenicity independent of splicing defects in a novel murine model by Brijesh Sathian et al. Brijesh Sathian等人在一种新的小鼠模型中，细胞质RBM20功能获得诱导心房心律失常，不依赖于剪接缺陷。

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-08-19 DOI: 10.1016/j.yjmcc.2025.08.006

Kensuke Ihara

引用次数: 0

A brief history of circadian time in the heart 心脏昼夜节律时间简史

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology

Pub Date : 2025-08-19 DOI: 10.1016/j.yjmcc.2025.08.005

Martin E. Young , Vanya Khanna , Mallory Metcalfe , Niruththaan Rameshkumar , Sarah Harington , Leo H. Li , Janan Shoja Doost , Heinrich Taegtmeyer , Tami A. Martino

This review tracks the discovery of circadian biology in cardiovascular science, starting with early clinical observations of daily changes in heart rate, blood pressure, and cardiovascular events. These patterns suggested that time of day matters, but it was not until the past two decades that the mechanisms and knowledge translation of these rhythms were uncovered. We describe the heart's intrinsic circadian properties and importantly how this leads to regulation of cardiac gene and protein expression, neuroendocrine and vascular rhythms, metabolism, cellular electrophysiology, and cell signaling pathways. Next, we explore emerging themes, including the impact of circadian timing on ischemic injury, cardiac aging, and trends in circadian desynchrony, sex, and interorgan crosstalk. Building on these discoveries, circadian medicine is beginning to reshape clinical care including timing of surgery, chronotherapies, biomarkers, ICU design, novel molecular drugs targeting the circadian clock, the role of the microbiome and time restricted eating, the new field of rest, and the concept of One Health and applications to veterinary medicine. Looking ahead we address new frontiers such as epigenetics, gene editing, and spaceflight. Together, these advances offer a roadmap for how circadian rhythms can be harnessed to improve cardiovascular health and disease outcomes, supporting longer and healthier lives.

本文回顾了心血管科学中昼夜节律生物学的发现，从早期临床观察心率、血压和心血管事件的日常变化开始。这些模式表明，一天中的时间很重要，但直到过去二十年，这些节律的机制和知识转化才被揭示出来。我们描述了心脏内在的昼夜节律特性，以及这如何导致心脏基因和蛋白质表达、神经内分泌和血管节律、代谢、细胞电生理和细胞信号传导途径的调节。接下来，我们将探讨新出现的主题，包括昼夜节律对缺血性损伤、心脏老化的影响，以及昼夜节律不同步、性别和器官间串扰的趋势。在这些发现的基础上，昼夜节律医学开始重塑临床护理，包括手术时机、时间疗法、生物标志物、ICU设计、针对昼夜节律钟的新型分子药物、微生物组的作用和限时饮食、新的休息领域，以及“同一个健康”的概念及其在兽医学中的应用。展望未来，我们将探讨表观遗传学、基因编辑和太空飞行等新领域。总之，这些进展为如何利用昼夜节律改善心血管健康和疾病结局、支持更长寿、更健康的生活提供了路线图。

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