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“Circulating Inflammation” and the Plasma Proteome in Heart Failure With Preserved Ejection Fraction 射血分数保留型心力衰竭的 "循环炎症 "和血浆蛋白质组
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-09-01 DOI: 10.1016/j.jacbts.2024.07.004
Thomas M. Vondriska PhD , David J. Lefer PhD
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引用次数: 0
TRIM55: An Enemy at the Post-MI Border? TRIM55：后 MI 边界的敌人？
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-09-01 DOI: 10.1016/j.jacbts.2024.06.009
Marco Andreis MD , Nazareno Paolocci MD, PhD
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引用次数: 0
Towards Metabolomic-Based Precision Approaches for Classifying and Treating Heart Failure 基于代谢组学的心力衰竭分类和治疗精准方法
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-09-01 DOI: 10.1016/j.jacbts.2024.04.008
Virginia S. Hahn MD , Senthil Selvaraj MD, MS, MA , Kavita Sharma MD , Svati H. Shah MD, MHS
Both heart failure and cardiometabolic disease are on the rise, and abnormal cardiac and peripheral metabolism are central to the syndrome of heart failure. Advances in metabolomic profiling have improved our understanding of the heart’s metabolic flexibility in patients with and without heart failure. Prior studies have noted patients with heart failure display metabolomic profiles associated with marked abnormalities in the metabolism of fatty acids, branched-chain amino acids, ketones, and glucose compared with control subjects. Metabolomics can highlight specific pathways that are dysregulated; however, other metabolites beyond those related to fuel metabolism may also play a role in precision-medicine approaches. Novel approaches include metabolic flux studies, spatial and single-cell analysis, serial monitoring of treatment response, and integration with other -omics data. The goal of these innovative approaches should be to harness metabolomic technologies to affect precision care for patients with heart failure.
心力衰竭和心脏代谢疾病都呈上升趋势，而心脏和外周代谢异常是心力衰竭综合征的核心。代谢组学分析技术的进步提高了我们对心力衰竭患者和非心力衰竭患者心脏代谢灵活性的认识。先前的研究指出，与对照组相比，心力衰竭患者的代谢组学特征与脂肪酸、支链氨基酸、酮体和葡萄糖代谢的明显异常有关。代谢组学可以突出显示失调的特定通路；然而，除了与燃料代谢相关的代谢物外，其他代谢物也可能在精准医疗方法中发挥作用。新方法包括代谢通量研究、空间和单细胞分析、治疗反应的连续监测以及与其他组学数据的整合。这些创新方法的目标应该是利用代谢组学技术影响心衰患者的精准治疗。
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引用次数: 0
The Imperative to Enhance Cost-Effectiveness for Cardiovascular Therapeutic Development 提高心血管治疗药物开发的成本效益势在必行
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-08-01 DOI: 10.1016/j.jacbts.2023.12.005

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Therapeutic agents, such as those that lower low-density lipoprotein cholesterol, have been a critical factor in mitigating CVD event risk and demonstrate the important role that drug discovery plays in reducing morbidity and mortality. However, rapidly rising development costs, diminishing returns, and an increasingly challenging regulatory environment have all contributed to a declining number of cardiovascular (CV) therapeutic agents entering the health care marketplace. For pharmaceutical companies, a traditional cardiovascular outcomes trial (CVOT) can be a major financial burden and impediment to CV agent development. They can take as long as a decade to conduct, delaying potential investment return while carrying risk of failure. For patients, lengthy CVOTs delay drug accessibility. Without cost-effective CVOTs, drug innovation may be compromised, with CV patients bearing the consequences. This paper reviews potential approaches for making CV drug development more cost-effective.

心血管疾病（CVD）是导致全球死亡的主要原因。治疗药物，如降低低密度脂蛋白胆固醇的药物，一直是降低心血管疾病事件风险的关键因素，也证明了药物研发在降低发病率和死亡率方面的重要作用。然而，快速上升的研发成本、不断降低的回报率以及日益严峻的监管环境都导致进入医疗市场的心血管（CV）治疗药物数量不断减少。对于制药公司来说，传统的心血管治疗效果试验（CVOT）可能是一项重大的经济负担，并阻碍心血管药物的开发。这些试验可能需要长达十年的时间才能完成，在推迟潜在投资回报的同时还存在失败的风险。对患者来说，漫长的 CVOT 会推迟药物的可及性。如果没有具有成本效益的 CVOT，药物创新可能会受到影响，后果将由冠心病患者承担。本文回顾了提高 CV 药物开发成本效益的潜在方法。
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引用次数: 0
A Murine Model of mRNA COVID-19 Vaccine-Induced Myocarditis mRNA COVID-19 疫苗诱发心肌炎的小鼠模型
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-08-01 DOI: 10.1016/j.jacbts.2024.05.005
Sander Eens MSc , Manon Van Hecke MD , Siel Van den Bogaert PharmD , Kasper Favere MD , Nathalie Cools MSc, PhD , Erik Fransen MSc, PhD , Tania Roskams MD, PhD , Hein Heidbuchel MD, PhD , Pieter-Jan Guns PharmD, PhD
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引用次数: 0
Reassessing the Mechanisms of PLN-R14del Cardiomyopathy 重新评估 PLN-R14del 心肌病的发病机制
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-08-01 DOI: 10.1016/j.jacbts.2024.02.017

The phospholamban (PLN) pathogenic gene variant, p.Arg14del (PLN-R14del), can lead to dilated and arrhythmogenic cardiomyopathy, resulting in heart failure. PLN-R14del cardiomyopathy has been conceptualized as a disease caused by sarco/endoplasmic reticulum calcium adenosine triphosphatase 2a (SERCA2a) superinhibition. However, recent studies raised controversy regarding the effect of PLN-R14del on SERCA activity and revealed a prominent role for abnormal PLN protein distribution and sarco/endoplasmic reticulum disorganization as underlying disease mechanism. Strategies targeting sarco/endoplasmic reticulum malformation may, therefore, prove more effective than SERCA activity modulation. This review reassesses the disease mechanisms of PLN-R14del cardiomyopathy and emphasizes the importance of dissecting the underlying molecular mechanisms to uncover targets for innovative treatments.

磷脂酰班（PLN）致病基因变异p.Arg14del（PLN-R14del）可导致扩张性和心律失常性心肌病，导致心力衰竭。PLN-R14del 心肌病一直被认为是一种由肌浆/内质网钙腺苷三磷酸酶 2a（SERCA2a）超抑制引起的疾病。然而，最近的研究引发了有关 PLN-R14del 对 SERCA 活性影响的争议，并揭示了 PLN 蛋白分布异常和肌浆/内质网紊乱作为潜在疾病机制的重要作用。因此，针对肌浆/内质网畸形的策略可能比调节 SERCA 活性更有效。本综述重新评估了 PLN-R14del 心肌病的发病机制，并强调了剖析潜在分子机制以发现创新治疗靶点的重要性。
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引用次数: 0
Novel Mechanisms of Postural Hyperventilation in Postural Orthostatic Tachycardia Syndrome 体位性正位性心动过速综合征中体位性过度通气的新机制
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-08-01 DOI: 10.1016/j.jacbts.2024.05.010
Stefanos Zafeiropoulos MD, PhD , Stavros Stavrakis MD, PhD
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引用次数: 0
Beta Testing New Roles of Cyclic Guanosine Monophosphate in Cardiac Myocyte Contractility 测试环磷酸鸟苷在心肌细胞收缩力中的新作用
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-08-01 DOI: 10.1016/j.jacbts.2024.05.012
Robert M. Blanton MA, MD
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引用次数: 0
Full Issue PDF 全期 PDF
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-08-01 DOI: 10.1016/S2452-302X(24)00284-5
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引用次数: 0
How Clonal Hematopoiesis Can Predict Treatment Response in Patients With Dilated Cardiomyopathy 克隆性造血如何预测扩张型心肌病患者的治疗反应
IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
JACC: Basic to Translational Science
Pub Date : 2024-08-01 DOI: 10.1016/j.jacbts.2024.06.002
Maurits A. Sikking MD , Job A.J. Verdonschot MD, PhD
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引用次数: 0
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