A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease.

IF 35.5 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Circulation Pub Date : 2024-11-21 DOI:10.1161/CIRCULATIONAHA.123.067156

Wouter Derks, Julian Rode, Sofia Collin, Fabian Rost, Paula Heinke, Anjana Hariharan, Lauren Pickel, Irina Simonova, Enikő Lázár, Evan Graham, Ramadan Jashari, Michaela Andrä, Anders Jeppsson, Mehran Salehpour, Kanar Alkass, Henrik Druid, Christos P Kyriakopoulos, Iosif Taleb, Thirupura S Shankar, Craig H Selzman, Hesham Sadek, Stefan Jovinge, Lutz Brusch, Jonas Frisén, Stavros Drakos, Olaf Bergmann

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Abstract

Background: Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.

Methods: We determined cardiomyocyte renewal in 52 patients with advanced heart failure, 28 of whom received left ventricular assist device support. We measured the concentration of nuclear bomb test-derived ¹⁴C in cardiomyocyte genomic DNA and performed mathematical modeling to establish cardiomyocyte renewal in heart failure with and without LVAD unloading.

Results: We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18 to 50× lower compared with the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart.

Conclusions: Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.

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人类心脏病中潜伏的心肌细胞再生潜能

背景：成人心脏中的心肌细胞具有再生能力，年更新率≈0.5%。人类心肌细胞的这种再生能力在心力衰竭时是否会被利用一直存在争议：我们测定了 52 名晚期心力衰竭患者的心肌细胞再生能力，其中 28 人接受了左心室辅助装置支持。我们测量了心肌细胞基因组 DNA 中源于核弹试验的 14C 的浓度，并通过数学建模确定了心衰患者在有左心室辅助器卸载和无左心室辅助器卸载情况下的心肌细胞更新情况：结果：我们发现，与健康心脏相比，终末期心力衰竭患者的心肌细胞生成率低 18 至 50 倍。然而，接受左心室支持装置治疗的患者在心脏功能和结构方面均有显著改善，其心肌细胞更新率与健康心脏相比增加了 6 倍以上：结论：我们的研究结果揭示了人类心脏病患者心肌细胞再生的巨大潜力，可用于治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation 医学-外周血管病

CiteScore

45.70

自引率

2.10%

发文量

1473

审稿时长

2 months

期刊介绍： Circulation is a platform that publishes a diverse range of content related to cardiovascular health and disease. This includes original research manuscripts, review articles, and other contributions spanning observational studies, clinical trials, epidemiology, health services, outcomes studies, and advancements in basic and translational research. The journal serves as a vital resource for professionals and researchers in the field of cardiovascular health, providing a comprehensive platform for disseminating knowledge and fostering advancements in the understanding and management of cardiovascular issues.