Journal of molecular and cellular cardiology plus最新文献_第3页

Ac-SDKP and eplerenone confer additive cardioprotection against angiotensin II-induced cardiac injury in C57BL/6J mice Ac-SDKP和eperenone对C57BL/6J小鼠血管紧张素ii诱导的心脏损伤具有附加的心脏保护作用

IF 2.2

Journal of molecular and cellular cardiology plus

Pub Date : 2025-09-19 DOI: 10.1016/j.jmccpl.2025.100485

Suhail Hamid , Sarah Sarkar , Hongmei Peng , Matrougui Khalid , Pablo A. Ortiz , Jiang Xu , Tang-Dong Liao , Robert A. Knight , Nour-Eddine Rhaleb

Eplerenone, a mineralocorticoid receptor antagonist, is an anti-hypertensive and cardioprotective drug. We showed that N-Acetyl-Seryl-Aspartyl-Proline (Ac-SDKP) exerts beneficial effects on the heart. Whether Ac-SDKP provides additional cardioprotective effects if combined with eplerenone in angiotensin II (Ang II)-induced hypertension remains unknown. Male C57BL/6J mice were treated with either sham, Ang II (2.9 mg/kg/day, s.c.), Ang II + Ac-SDKP (1.6 mg/kg/day, s.c.), Ang II + Eplerenone (150 mg/kg/day in mouse chow), or Ang II + Ac-SDKP + Eplerenone. Treatment lasted for eight weeks. Systolic blood pressure (SBP) measurements were taken weekly. Echocardiography (Echo) and magnetic resonance imaging (MRI) were performed at the end of the experiment. SBP was increased in all mice with Ang II and was not affected by any treatment. Posterior wall thickness (PWT) and left ventricular (LV) mass were increased in Ang II–treated groups. LV mass was not significantly affected by treatment, but PWT was reduced by both monotherapies and showed the greatest reduction with combined Ac-SDKP and eplerenone. Ejection fraction (EF) decreased in the Ang II group compared to the sham group. EF increased with all treatments (MRI), and there was a further significant increase in EF for mice treated with Ac-SDKP + Eplerenone compared to those receiving a single treatment (Echo). Our data indicate that treatment with Ac-SDKP or Eplerenone improves cardiac function in Ang II-induced hypertension, and supplying Ac-SDKP to Eplerenone provides additive, not synergistic, cardioprotective effects. These beneficial effects were associated with decreased myocardial collagen accumulation, CD68-positive macrophage infiltration, and the expression of CHOP, an endoplasmic reticulum stress mediator. Ac-SDKP could be an effective supplementary treatment alongside Eplerenone for managing hypertension-associated cardiac damage and dysfunction.

依普利酮是一种矿物皮质激素受体拮抗剂，是一种抗高血压和心脏保护药物。我们发现n -乙酰- seryl -天冬氨酸-脯氨酸（Ac-SDKP）对心脏有有益作用。在血管紧张素II （Ang II）诱导的高血压中，Ac-SDKP与依普利酮联用是否能提供额外的心脏保护作用尚不清楚。雄性C57BL/6J小鼠分别给予假药、Ang II （2.9 mg/kg/day, s.c）、Ang II + Ac-SDKP （1.6 mg/kg/day, s.c）、Ang II + Eplerenone （150 mg/kg/day，小鼠饲料）或Ang II + Ac-SDKP + Eplerenone。治疗持续了8周。每周测量收缩压（SBP）。实验结束时进行超声心动图（Echo）和磁共振成像（MRI）检查。所有小鼠的收缩压均升高，且不受任何治疗的影响。angii治疗组后壁厚度（PWT）和左心室质量（LV）均增加。左室质量没有受到治疗的显著影响，但两种单一治疗均可减少PWT，并以Ac-SDKP和eperenone联合治疗的减少幅度最大。与假手术组相比，Ang II组的射血分数（EF）降低。EF随所有治疗（MRI）而增加，与接受单一治疗（Echo）的小鼠相比，Ac-SDKP + Eplerenone治疗的小鼠EF进一步显著增加。我们的数据表明，Ac-SDKP或Eplerenone治疗可改善Ang ii诱导的高血压患者的心功能，并且将Ac-SDKP与Eplerenone结合提供附加而非协同的心脏保护作用。这些有益作用与减少心肌胶原积累、cd68阳性巨噬细胞浸润和内质网应激介质CHOP的表达有关。Ac-SDKP可能是与依普利酮一起治疗高血压相关心脏损伤和功能障碍的有效补充治疗。

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引用次数: 0

Single-cell dynamics reveal a stress-induced decision between hypertrophy and apoptosis in neonatal rat cardiomyocytes 单细胞动力学揭示了应激诱导的新生大鼠心肌细胞肥大和凋亡之间的决定

IF 2.2

Journal of molecular and cellular cardiology plus

Pub Date : 2025-09-16 DOI: 10.1016/j.jmccpl.2025.100484

Bryan Chun , Lavie Ngo , Jeffrey J. Saucerman

Cardiomyocyte hypertrophy and apoptosis underlie cardiomyopathies and heart failure. While previous studies have reported both hypertrophy and apoptosis at the population level, how individual cells commit to these distinct analog and digital fates is unclear. To elucidate how individual cells decide to grow and/or die, we developed a high-content microscopy approach to track single-cell dynamics of neonatal rat cardiomyocytes. Even untreated cells exhibited substantial single-cell variability in growth and death. Uniform treatments of staurosporine or phenylephrine induced distinctive morphological programs resulting in apoptosis and hypertrophy, respectively, but only in cell subpopulations. Increasing concentrations of the β-adrenergic receptor agonist isoproterenol caused a population-level biphasic induction of hypertrophy and then apoptosis, consistent with either apoptosis in the most hypertrophic cells (a grow-and-die model) or an early decision between hypertrophy and delayed apoptosis (a grow-or-die model). By tracking single-cell fates, we found that when stressed with either isoproterenol or phenylephrine, individual cells that hypertrophy are protected from later apoptosis. Further, caspase 3 inhibition shifted the single-cell probability from apoptosis to hypertrophy fates. Machine learning models found that a cell's initial size and DNA content or condensation could predict a cell's bias for hypertrophy or apoptosis. Together, these data support a grow-or-die conceptual model for cardiomyocyte decisions. This single-cell profiling method for tracking joint analog-digital cell decisions reveals that despite hypertrophy and apoptosis co-occurring at the population level, individual cardiomyocytes decide early whether to grow or die.

心肌细胞肥大和凋亡是心肌病和心力衰竭的基础。虽然先前的研究已经报道了在群体水平上的肥大和凋亡，但个体细胞如何承担这些不同的模拟和数字命运尚不清楚。为了阐明单个细胞如何决定生长和/或死亡，我们开发了一种高含量显微镜方法来跟踪新生大鼠心肌细胞的单细胞动力学。即使未经处理的细胞在生长和死亡方面也表现出明显的单细胞变异性。staurosporine或phenylephrine的统一处理分别诱导了不同的形态学程序，导致细胞凋亡和肥大，但仅在细胞亚群中。增加β-肾上腺素能受体激动剂异丙肾上腺素的浓度可引起群体水平的肥厚和细胞凋亡双相诱导，这与大多数肥厚细胞的凋亡（生长-死亡模型）或肥厚和延迟细胞凋亡之间的早期决定（生长-死亡模型）相一致。通过追踪单细胞的命运，我们发现，在异丙肾上腺素或苯肾上腺素的胁迫下，肥大的单个细胞受到保护，免受后来的凋亡。此外，caspase 3的抑制使单细胞的可能性从凋亡转变为肥大。机器学习模型发现，细胞的初始大小和DNA含量或凝结可以预测细胞的肥大或凋亡倾向。总之，这些数据支持心肌细胞决策的生长或死亡概念模型。这种用于跟踪模拟-数字联合细胞决策的单细胞分析方法表明，尽管肥大和凋亡在群体水平上共同发生，但单个心肌细胞很早就决定了是生长还是死亡。

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引用次数: 0

Systemic administration of analgesic buprenorphine, but not carprofen, affects cardiomyocyte contractility in rodents 全身给药丁丙诺啡，而不是卡洛芬，会影响啮齿类动物的心肌细胞收缩力

IF 2.2

Journal of molecular and cellular cardiology plus

Pub Date : 2025-09-10 DOI: 10.1016/j.jmccpl.2025.100482

Inez Duursma , Valentijn Jansen , Nicole Zaat , Tyler J. Kirby , Jolanda van der Velden , Diederik W.D. Kuster

Rodents are often used in cardiac research, where they undergo a wide variety of procedures. To ensure animal welfare, the rodents are often analgesized before, during and/or after a procedure. Contractility measurements in isolated murine cardiomyocytes are an often used method to assess function; however, little is known about the effects of analgesia on this. Therefore, we investigated the effect of systemic injection of a non-steroidal anti-inflammatory drug, carprofen (N = 3 mice, n = 273 CMs; N = 3 rats, n = 241 CMs) and an opioid, buprenorphine (N = 4 mice, n = 326 CMs; N = 4 rats, n = 308 CMs) on isolated cardiomyocytes using unloaded contractility measurements. We found that buprenorphine prolongs the relaxation of cardiomyocytes, an effect confound to the first 3 h post-isolation, whereas carprofen does not affect contractility. As analgesia might influence the stress response, we assessed the influence of carprofen and buprenorphine on the β-adrenergic receptor (AR) response. The response of cardiomyocytes to both a β-AR agonist and antagonist was not affected by carprofen or buprenorphine. In vitro addition of the analgesics to rat cardiomyocytes (N = 3 rats, n = 197 CMs saline, n = 214 CMs carprofen, n = 211 CMs buprenorphine) revealed that the effect of buprenorphine on contractility is caused by a systemic response rather than a direct response of cardiomyocytes specifically. Collectively, our results suggest that carprofen and buprenorphine do not affect isolated cardiomyocyte contractility if measurements are performed at least 4 h post-isolation.

啮齿动物经常被用于心脏研究，在那里他们经历了各种各样的程序。为了确保动物的福利，啮齿动物通常在手术之前、期间和/或之后进行镇痛。在离体小鼠心肌细胞中测量收缩力是一种常用的评估功能的方法；然而，我们对镇痛药在这方面的作用知之甚少。因此，我们研究了全身注射非甾体抗炎药卡洛芬（N = 3只小鼠，N = 273 CMs; N = 3只大鼠，N = 241 CMs）和阿片类药物丁丙诺啡（N = 4只小鼠，N = 326 CMs; N = 4只大鼠，N = 308 CMs）对离体心肌细胞的影响。我们发现丁丙诺啡延长心肌细胞的松弛，这种作用在分离后的前3小时出现，而卡洛芬不影响收缩力。由于镇痛可能影响应激反应，我们评估了卡洛芬和丁丙诺啡对β-肾上腺素能受体（AR）反应的影响。心肌细胞对β-AR激动剂和拮抗剂的反应不受卡洛芬或丁丙诺啡的影响。体外给药大鼠心肌细胞（N = 3只大鼠，N = 197 cm生理盐水，N = 214 cm卡洛芬，N = 211 cm丁丙诺啡）实验表明，丁丙诺啡对心肌收缩力的影响是全身反应，而不是心肌细胞特异性的直接反应。总的来说，我们的结果表明，如果在分离后至少4小时进行测量，卡洛芬和丁丙诺啡不会影响分离的心肌细胞收缩力。

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引用次数: 0

Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression Med13和Med13L：基础心功能和基因表达的关键冗余参与者

IF 2.2

Journal of molecular and cellular cardiology plus

Pub Date : 2025-09-01 DOI: 10.1016/j.jmccpl.2025.100481

Kayla M. Henry , Richard N. Gardner , Alexis M. Oppman , Nastaran Daneshgar , Mariela Rosales , Ines Martins , Kedryn K. Baskin , Chad E. Grueter

Background

Previous studies have linked mutations in the Mediator complex, specifically Mediator 13 (Med13) and Mediator 13-like (Med13L), with both congenital heart defects and cardiovascular diseases. Med13 and Med13L are mutually exclusive paralogs within the kinase submodule of the Mediator complex that have been shown to have partially redundant functions in embryonic development and transcription, but their combined roles have not been investigated in the adult heart. We investigated the critical yet redundant roles of Med13 and Med13L in adult murine cardiomyocytes for basal cardiac function.

Methods

We generated an inducible Med13 and Med13L cardiomyocyte-specific knockout mouse model to investigate Med13 and Med13L regulation of cardiac function and transcription. We performed RNAseq on mice four weeks after the start of tamoxifen to identify changes in gene expression. Differentially expressed genes were compared across cardiac knockouts of Med13/13L, Med13, Med12, Med1, and Med30 elucidating similar mechanisms of cardiac dysfunction.

Results

Med13/13L knockout resulted in decreased cardiac function leading to lethal heart failure in a median timeframe of 6 weeks from the start of tamoxifen. There is significant gene dysregulation after Med13/13L knockout with similar gene dysregulation of fibrotic pathways and calcium handling across Mediator cardiac knockouts.

Conclusions

Med13 and Med13L function partially redundantly within the heart to maintain basal cardiac function and transcription, as well as redundancies within cardiac phenotypes related to mediator complex disruptions.

先前的研究已经将中介复合物的突变，特别是中介13 （Med13）和中介13样（Med13L）与先天性心脏缺陷和心血管疾病联系起来。Med13和Med13L是中介复合物激酶亚模块中相互排斥的类似物，已被证明在胚胎发育和转录中具有部分冗余功能，但它们在成人心脏中的联合作用尚未被研究。我们研究了Med13和Med13L在成年小鼠心肌细胞中对基础心功能的关键但冗余的作用。方法建立可诱导的Med13和Med13L心肌细胞特异性敲除小鼠模型，研究Med13和Med13L对心功能和转录的调节作用。我们在服用他莫昔芬4周后对小鼠进行了RNAseq，以确定基因表达的变化。我们比较了Med13/ 13l、Med13、Med12、Med1和Med30基因敲除的差异表达基因，阐明了类似的心功能障碍机制。结果med13 / 13l基因敲除导致心功能下降，在他莫昔芬开始治疗的中位时间框架6周内导致致死性心力衰竭。Med13/13L基因敲除后存在显著的基因失调，在整个中介心脏敲除中，纤维化途径和钙处理的基因失调也相似。结论：med13和Med13L在心脏内部分冗余地发挥作用，以维持基础心脏功能和转录，以及与介质复合物中断相关的心脏表型冗余。

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引用次数: 0

JMCC plus receives first impact factor JMCC plus获得第一影响因子

IF 2.2

Journal of molecular and cellular cardiology plus

Pub Date : 2025-09-01 DOI: 10.1016/j.jmccpl.2025.100480

Davor Pavlovic , Rebekah Gundry

引用次数: 0

Cocaine and the heart – bad news for risk/reward 可卡因和心脏——风险/回报的坏消息

IF 2.2

Journal of molecular and cellular cardiology plus

Pub Date : 2025-09-01 DOI: 10.1016/j.jmccpl.2025.100477

Jules C. Hancox, Andrew F. James

引用次数: 0

Sex-specific human electromechanical multiscale in-silico models for virtual therapy evaluation 用于虚拟治疗评估的性别特异性人类机电多尺度计算机模型

IF 2.2

Journal of molecular and cellular cardiology plus

Pub Date : 2025-08-09 DOI: 10.1016/j.jmccpl.2025.100479

Maxx Holmes , Zhinuo Jenny Wang , Ruben Doste , Julia Camps , Hector Martinez-Navarro , Hannah Smith , Jakub Tomek , Blanca Rodriguez

Background

Women are under-represented in cardiovascular research, leading to poorer outcomes. Investigating sex-differences in electromechanical function is essential for improving therapy evaluation. This study presents sex-specific human cellular and biventricular electromechanical models for mechanistic investigation of sex-differences in therapeutic response.

Methods

Protein genomic expression data from healthy human myocytes calibrated sex-specific electrophysiological models, integrated into biventricular models with male and female anatomies. Multi-scale validation utilised sex-specific clinical and experimental datasets, including responses to drug action. Ionic mechanisms underlying sex-differences in drug response were explored.

Results

Simulations showed agreement with clinical ECGs, including QTc intervals (Male: 312 ms; Female: 339 ms), and T-wave amplitude (6–9 % difference). Mechanical biomarkers (LVEF, Female: 68 %; Male: 50 %) matched sex-stratified UK Biobank data (n = 806; 46 % Male). ECG sex-characteristics were driven by ionic differences, while mechanical differences stemmed from anatomical and ionic differences. Simulations predicted exacerbated QTc prolongation under Dofetilide in women (54–78 % higher than males) and T-wave amplitude reduction in men (max: −0.25 mV). Verapamil increased T-wave amplitude in females and decreased it in males, without affecting QTc. Simulations demonstrated reduced repolarisation reserve and increased QTc susceptibility in women via hERG inhibition, while enhanced calcium buffering protected against T-wave amplitude loss. LVEF changes in response to calcium block were more sensitive to anatomical differences between male and female than to ionic sex phenotypes.

Conclusion

Sex differences in repolarisation reserve, calcium handling, and anatomy are key factors underpinning ECG and LVEF responses to drugs. Specifically, under calcium block, females showed more preserved LVEF, while under hERG block, females showed more QTc prolongation.

女性在心血管研究中的代表性不足，导致较差的结果。研究机电功能的性别差异对改善治疗评价至关重要。本研究提出了性别特异性的人类细胞和双心室机电模型，用于治疗反应性别差异的机制研究。方法将健康人类肌细胞的蛋白质基因组表达数据整合到具有男性和女性解剖结构的双心室模型中，校准性别特异性电生理模型。多尺度验证利用了性别特异性临床和实验数据集，包括对药物作用的反应。探讨了药物反应性别差异的离子机制。结果模拟结果与临床心电图一致，包括QTc间隔(男性：312 ms；女性：339 ms)，和t波振幅（6 - 9%的差异）。机械生物标志物(LVEF，女性：68%；男性：50%)匹配性别分层的UK Biobank数据(n = 806；46%男性)。ECG性别特征由离子差异驱动，而力学差异源于解剖和离子差异。模拟预测，服用多非利特后，女性QTc延长（比男性高54 - 78%），男性t波幅度降低（最大：- 0.25 mV）。维拉帕米增加了女性的t波振幅，降低了男性的t波振幅，但不影响QTc。模拟表明，通过hERG抑制，女性的重极化储备减少，QTc敏感性增加，而增强的钙缓冲可以防止t波振幅损失。LVEF对钙阻滞反应的变化对男女解剖差异比对离子性别表型更敏感。结论两性在复极储备、钙处理和解剖学上的差异是影响ECG和LVEF对药物反应的关键因素。其中，钙阻断下雌性LVEF保存较多，而hERG阻断下雌性QTc延长较多。

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引用次数: 0

Generation and evaluation of a novel PI3K-targeting gene therapy in the failing mouse heart and healthy sheep heart 一种新的pi3k靶向基因治疗衰竭小鼠心脏和健康绵羊心脏的产生和评估

IF 2.2

Journal of molecular and cellular cardiology plus

Pub Date : 2025-07-31 DOI: 10.1016/j.jmccpl.2025.100478

Sebastian Bass-Stringer , Daniel G. Donner , Clive N. May , Aya Matsumoto , Emma I. Masterman , Aascha A. D'Elia , Yi Ching Chen , Helen Kiriazis , Jieting Luo , Roger Chooi , Clara Liu Chung Ming , Paul Gregorevic , Colleen J. Thomas , Bianca C. Bernardo , Kate L. Weeks , Julie R. McMullen

Heart failure (HF) remains a clinical challenge with cardiac dysfunction typically progressing even with treatment, and heart transplants only available to small numbers. We previously identified phosphoinositide 3-kinase (PI3K, p110α) as a master regulator of exercise-induced cardioprotection, and showed that gene therapy, incorporating a constitutively active form of PI3K (caPI3K) improved function of the failing mouse heart. However, this approach was not cardiac-specific and the gene therapy was challenging to manufacture. The aim of this study was to develop new PI3K-based gene therapies with more optimal properties for clinical translation. We generated and assessed adeno-associated viruses (AAV6) encoding various PI3K constructs, with different enhancers, promoters and transgene components in healthy adult male mice. The most promising AAV construct based on AAV expression, cardiac-specificity, and ease of manufacture contained a cardiac troponin T (cTnT) promoter together with a small region of the regulatory subunit of PI3K (iSH2), and an intron from the β-globin gene which enhances transcription (IVS2). This AAV (1 × 10¹², 2 × 10¹² vg) was administered to mice with myocardial ischemia/reperfusion injury (I/R: 1 h ischemia with reperfusion; AAV delivered 24 h post-I/R). Direct cardiac injections of PI3K-based AAVs were also performed in healthy adult female sheep. I/R mouse hearts treated with the AAV6-cTnT-IVS2-iSH2 displayed increased phosphorylation of Akt, but no improvement in cardiac function or structure was observed. AAV6-cTnT-IVS2-iSH2 successfully transduced healthy sheep hearts which increased endogenous PI3K catalytic activity. Further testing/optimization of the AAV (time of delivery and/or duration) will be required to assess the therapeutic potential of this approach.

心力衰竭（HF）仍然是一个临床挑战，即使治疗，心脏功能障碍通常也会恶化，心脏移植只适用于少数人。我们之前确定了磷酸肌肽3-激酶（PI3K, p110α）是运动诱导的心脏保护的主要调节因子，并表明基因治疗，包括组成活性形式的PI3K （caPI3K）改善了衰竭小鼠的心脏功能。然而，这种方法不是针对心脏的，而且这种基因疗法的制造具有挑战性。本研究的目的是开发新的基于pi3的基因疗法，具有更理想的临床转化特性。我们在健康成年雄性小鼠中生成并评估了编码多种PI3K构建体、具有不同增强子、启动子和转基因成分的腺相关病毒（AAV6）。基于AAV表达、心脏特异性和易于制造的最有希望的AAV构建物包含一个心脏肌钙蛋白T （cTnT）启动子、PI3K调控亚基的一个小区域（iSH2）和一个来自β-珠蛋白基因的内含子，该内含子可促进转录（IVS2）。将AAV （1 × 1012,2 × 1012vg）给予心肌缺血/再灌注损伤小鼠(I/R：缺血再灌注1 h；AAV在i /R后24小时交付)。在健康成年母羊中也进行了基于pi3的aav直接心脏注射。AAV6-cTnT-IVS2-iSH2处理的I/R小鼠心脏显示Akt磷酸化增加，但未观察到心脏功能或结构的改善。AAV6-cTnT-IVS2-iSH2成功转导了健康绵羊心脏，增加了内源性PI3K的催化活性。需要进一步测试/优化AAV（给药时间和/或持续时间）来评估该方法的治疗潜力。

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引用次数: 0

Current status and challenges of multi-omics research using animal models of atherosclerosis 动脉粥样硬化动物模型多组学研究现状与挑战

Journal of molecular and cellular cardiology plus

Pub Date : 2025-07-10 DOI: 10.1016/j.jmccpl.2025.100476

Tijana Mitić , Adriana Georgescu , Nicoleta Alexandru-Moise , Michael J. Davies , Cecile Vindis , Susana Novella , Eva Gerdts , Georgios Kararigas , Stephanie Bezzina Wettinger , Melissa M. Formosa , Brenda R. Kwak , Filippo Molica , Nuria Amigo , Andrea Caporali , Fernando de la Cuesta , Ignacio Fernando Hall , Angeliki Chroni , Fabio Martelli , Johannes A. Schmid , Paolo Magni , Dimitris Kardassis

Atherosclerosis is an underlying cause of cardiovascular diseases (CVD) which account for most deaths worldwide. Use of diverse preclinical models of atherosclerosis has been implemental in understanding the underlying mechanisms, the implicated cell types, the genes and the molecules at play in the onset and progression of atherosclerotic plaques. Although significant research advancements have been made, further research is necessary to delve into factors influencing plaque types, site preference within the vasculature, interactions with adjacent tissues (liver, pancreas and perivascular adipose tissue), inflammation and sex-based disparities, among others. The conventional low throughput methodologies which concentrate on individual cells, genes or metabolites are inadequate to tackle the complex and heterogeneous nature of atherosclerosis. With recent advancement in multi-omics and bioinformatics, research approaches have illuminated a clearer understanding of atherosclerosis. Consequently, these advancements pave the path to design novel therapeutics to complement currently approved lipid-lowering and other effective treatments. In this article, we summarize and critically evaluate the findings derived from recent high throughput single- or multi-omic studies conducted in animal models of atherosclerosis. We also delve into the challenges associated with using experimental animals to model human atherosclerosis and contemplate the essential enhancements needed to better mimic human conditions. We further discuss the requirement of establishing a structured multi-omic database for atherosclerosis research, enabling broader access and utilisation within the scientific community.

动脉粥样硬化是心血管疾病（CVD）的潜在原因，心血管疾病占全世界死亡人数最多。多种临床前动脉粥样硬化模型的应用有助于理解动脉粥样硬化斑块发生和发展的潜在机制、相关细胞类型、基因和分子。尽管已经取得了重大的研究进展，但需要进一步的研究来深入研究影响斑块类型、血管内的部位偏好、与邻近组织（肝脏、胰腺和血管周围脂肪组织）的相互作用、炎症和性别差异等因素。传统的专注于单个细胞、基因或代谢物的低通量方法不足以解决动脉粥样硬化的复杂性和异质性。随着近年来多组学和生物信息学的进展，研究方法已经阐明了动脉粥样硬化的更清晰的认识。因此，这些进步为设计新的治疗方法铺平了道路，以补充目前批准的降脂和其他有效的治疗方法。在本文中，我们总结并批判性地评估了最近在动脉粥样硬化动物模型中进行的高通量单组或多组研究的结果。我们还深入研究了与使用实验动物来模拟人类动脉粥样硬化相关的挑战，并考虑了更好地模拟人类条件所需的基本增强。我们进一步讨论了为动脉粥样硬化研究建立一个结构化的多组学数据库的需求，使其在科学界得到更广泛的访问和利用。

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引用次数: 0

Cardiology's best friend: Using naturally occurring disease in dogs to understand heart disease in humans 心脏病学最好的朋友：用狗身上自然发生的疾病来了解人类的心脏病

Journal of molecular and cellular cardiology plus

Pub Date : 2025-07-04 DOI: 10.1016/j.jmccpl.2025.100474

W. Glen Pyle

Heart diseases are a leading cause of death globally. Laboratory and preclinical animal models of disease have been critical in advancing our understanding of the mechanisms of pathology, creating diagnostic tools, and developing therapeutic interventions. However, fundamental biological dissimilarities between humans and rodents limits their usefulness in research, and the induction of disease in an otherwise healthy animal creates unrealistic conditions under which diseases are typically studied. Dogs are at high risk of acquiring and dying from several naturally occurring heart disorders that also affect people. The spontaneous nature of these conditions, along with highly similar cardiovascular systems, offers unique opportunities to investigate cardiovascular disease in a more relevant model for humans. This review focuses on three common cardiac conditions that impact humans and dogs: dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and mitral valve disease – comparing mechanisms of disease, diagnostics, and treatments, to identify strengths and present limitations of their utility. It is noted that the benefits of this research are bidirectional, with the potential to translate knowledge and clinical tools used in veterinary medicine to human patients, and vice versa.

心脏病是全球死亡的主要原因。疾病的实验室和临床前动物模型对于促进我们对病理机制的理解、创建诊断工具和开发治疗干预措施至关重要。然而，人类和啮齿类动物之间基本的生物学差异限制了它们在研究中的用处，而且在健康的动物身上诱发疾病创造了不现实的条件，而疾病通常是在这种条件下进行研究的。狗有很高的风险患上和死于几种自然发生的心脏疾病，这些疾病也会影响到人类。这些疾病的自发性，以及高度相似的心血管系统，为在更相关的人类模型中研究心血管疾病提供了独特的机会。本文综述了影响人类和狗的三种常见心脏疾病：扩张型心肌病、致心律失常的右室心肌病和二尖瓣疾病——比较疾病的机制、诊断和治疗，以确定它们的优势和局限性。值得注意的是，这项研究的好处是双向的，有可能将兽医中使用的知识和临床工具转化为人类患者，反之亦然。

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引用次数: 0