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RBM15 Protects From Myocardial Infarction by Stabilizing NAE1 RBM15 通过稳定 NAE1 防止心肌梗死
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-05-01 DOI: 10.1016/j.jacbts.2024.01.017
Hao Cheng MD, PhD , Jian Wu MD, PhD , Linnan Li MD, PhD , Xiaoyue Song MD, PhD , Junqiang Xue MD, PhD , Yuekai Shi MD, PhD , Yunzeng Zou MD, PhD , Jianying Ma MD, PhD , Junbo Ge MD, PhD

RNA-binding proteins play multiple roles in several biological processes. However, the roles of RBM15—an important RNA-binding protein and a significant regulator of RNA methylation—in cardiovascular diseases remain elusive. This study aimed to investigate the biological function of RBM15 and its fundamental mechanisms in myocardial infarction (MI). Methylated RNA immunoprecipitation sequencing was used to explore the N6-methyladenosine (m6A) difference between MI and normal tissues. Our findings showed the elevated level of m6A in MI, and its transcription profile in both MI and normal tissues. RBM15 was the main regulator and its overexpression attenuated apoptosis in cardiomyocytes and improved cardiac function in mice after MI. Then, we used one target NEDD8 activating enzyme E1 subunit and its inhibitor (MLN4924) to investigate the impact of RBM15 targets on cardiomyocytes. Finally, the enhanced m6A methylation in the presence of RBM15 overexpression led to the increased expression and stability of NEDD8 activating enzyme E1 subunit. Our findings suggest that the enhanced m6A level is a protective mechanism in MI, and RBM15 is significantly upregulated in MI and promotes cardiac function. This study showed that RBM15 affected MI by stabilizing its target on the cell apoptosis function, which might provide a new insight into MI therapy.

RNA 结合蛋白在多个生物过程中发挥着多重作用。然而，RBM15--一种重要的 RNA 结合蛋白和 RNA 甲基化的重要调控因子--在心血管疾病中的作用仍不明确。本研究旨在探讨 RBM15 在心肌梗死（MI）中的生物学功能及其基本机制。研究采用甲基化 RNA 免疫沉淀测序技术，探讨了心肌梗死与正常组织中 N6-甲基腺苷（m6A）的差异。我们的研究结果表明，在心肌梗死中，m6A的水平升高，其在心肌梗死和正常组织中的转录情况也是如此。RBM15是主要的调控因子，其过表达可减轻心肌细胞的凋亡，并改善心肌梗死后小鼠的心脏功能。然后，我们利用一个靶点 NEDD8 激活酶 E1 亚基及其抑制剂（MLN4924）来研究 RBM15 靶点对心肌细胞的影响。最后，在 RBM15 过表达的情况下，m6A 甲基化增强导致 NEDD8 激活酶 E1 亚基的表达和稳定性增加。我们的研究结果表明，m6A水平的增强是心肌缺血的一种保护机制，而RBM15在心肌缺血中显著上调并促进心脏功能。本研究表明，RBM15通过稳定细胞凋亡功能靶点来影响心肌梗死，这可能为心肌梗死的治疗提供了新的思路。
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引用次数: 0
Stressing the Circle 强调圆
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-05-01 DOI: 10.1016/j.jacbts.2024.04.003
Simona Greco PhD, Fabio Martelli PhD
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引用次数: 0
Dysregulation of IL-6/MCP-1/STAT3 Axis IL-6/MCP-1/STAT3 轴失调
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-05-01 DOI: 10.1016/j.jacbts.2024.03.006
Andreas Mitsis MD, MSc, PhD(c) , Stergios Tzikas MD, PhD , George Kassimis MD, PhD
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引用次数: 0
Pulsatile ECMO 脉动 ECMO
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-04-01 DOI: 10.1016/j.jacbts.2024.02.015
Douglas E. Vincent BSME , Nader Moazami MD , David D’Alessandro MD , John F. Fraser MBChB, PhD , Silver Heinsar MD, PhD , Ellen T. Roche PhD , Brian C. Ayers MD , Manisha Singh PhD , Nina Langer MSME , Shriprasad R. Deshpande MBBS, MS , R.D.B. Jaquiss MD , Kiyotaka Fukamachi MD, PhD , Seyed Alireza Rabi MD, PhD , Asishana Osho MD, MPH , Taiyo Kuroda MD, PhD , Jamshid H. Karimov MD, PhD , Takuma Miyamoto MD, PhD , Palaniappan Sethu PhD , Guruprasad A. Giridharan PhD , Knut Kvernebo MD, PhD , Jack Copland MD
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引用次数: 0
Do Not Lose Your Nerves 不要失去理智
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-04-01 DOI: 10.1016/j.jacbts.2024.02.005
Katrin Schäfer MD
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引用次数: 0
JACC: Basic to Translational Science 2023 Thomas Force Young Investigator Award Winner JACC：基础到转化科学 2023 托马斯-费力青年研究员奖获得者
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-04-01 DOI: 10.1016/j.jacbts.2024.02.003
Douglas L. Mann MD (Editor-in-Chief: JACC: Basic to Translational Science)
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引用次数: 0
Cellular Senescence as a Targetable Risk Factor for Cardiovascular Diseases 细胞衰老是心血管疾病的靶向风险因素：治疗意义JACC Family Series
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-04-01 DOI: 10.1016/j.jacbts.2023.12.003
Manish Kumar MD , Pengyi Yan PhD , George A. Kuchel MD , Ming Xu PhD

The prevalence of cardiovascular diseases markedly rises with age. Cellular senescence, a hallmark of aging, is characterized by irreversible cell cycle arrest and the manifestation of a senescence-associated secretory phenotype, which has emerged as a significant contributor to aging, mortality, and a spectrum of chronic ailments. An increasing body of preclinical and clinical research has established connections between senescence, senescence-associated secretory phenotype, and age-related cardiac and vascular pathologies. This review comprehensively outlines studies delving into the detrimental impact of senescence on various cardiovascular diseases, encompassing systemic atherosclerosis (including coronary artery disease, stroke, and peripheral arterial disease), as well as conditions such as hypertension, congestive heart failure, arrhythmias, and valvular heart diseases. In addition, we have preclinical studies demonstrating the beneficial effects of senolytics—a class of drugs designed to eliminate senescent cells selectively across diverse cardiovascular disease scenarios. Finally, we address knowledge gaps on the influence of senescence on cardiovascular systems and discuss the future trajectory of strategies targeting senescence for cardiovascular diseases.

心血管疾病的发病率随着年龄的增长而明显上升。细胞衰老是衰老的标志之一，其特征是细胞周期不可逆转的停滞和衰老相关分泌表型的表现，衰老相关分泌表型已成为导致衰老、死亡率和一系列慢性疾病的重要因素。越来越多的临床前和临床研究证实了衰老、衰老相关分泌表型与年龄相关的心脏和血管病变之间的联系。本综述全面概述了有关衰老对各种心血管疾病的有害影响的研究，包括全身性动脉粥样硬化（包括冠状动脉疾病、中风和外周动脉疾病），以及高血压、充血性心力衰竭、心律失常和瓣膜性心脏病等疾病。此外，我们还开展了临床前研究，证明了衰老物质的有益作用，这类药物旨在有选择性地消除各种心血管疾病中的衰老细胞。最后，我们探讨了衰老对心血管系统影响方面的知识空白，并讨论了针对心血管疾病的衰老策略的未来发展轨迹。
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引用次数: 0
Introducing the 2024 THT Shark Tank Edition of JACC: Basic to Translational Science 介绍《JACC.THT Shark Tank》2024 版：从基础科学到转化科学
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-04-01 DOI: 10.1016/j.jacbts.2024.03.002
Douglas L. Mann MD
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引用次数: 0
Heart Failure Solutions 心力衰竭解决方案
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-04-01 DOI: 10.1016/j.jacbts.2024.02.010
Barry A. Borlaug MD , Mark Strong MBA, MSEE, BSEE
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引用次数: 0
NIHA-HF NIHA-HF
IF 9.7 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-04-01 DOI: 10.1016/j.jacbts.2024.02.011
Ying Chen PhD
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引用次数: 0
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