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慢性心理应激通过皮质酮-糖皮质激素受体-LAMA5轴诱导心肌细胞肥大。

Chronic Psychological Stress Induces Cardiomyocyte Hypertrophy Through Corticosterone-Glucocorticoid Receptor-LAMA5 Axis.

作者信息

Zhang Chuanjing, Song Yongfei, Jin Xiaojun, Xu Qingbo, Ye Honghua, Wu Zhuonan, Lin Hui, Hu Jiale, Huang Chen, Zhou Jianqing, Lian Jiangfang

机构信息

The Affiliated Lihuili Hospital of Ningbo University, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315000, China.

Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.

出版信息

Adv Sci (Weinh). 2025 Sep;12(36):e14659. doi: 10.1002/advs.202414659. Epub 2025 Jul 11.

DOI:10.1002/advs.202414659
PMID:40642838
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12463095/
Abstract

Chronic psychological stress is closely related to myocardial diseases, but the pathological processes and related mechanisms are not yet clear. In this study, 5 batches of animal experiments are conducted to reveal the pathological process of chronic psychological stress on the heart, and found that cardiomyocyte hypertrophy is an early manifestation of cardiac damage. Furthermore, it is discovered that corticosterone and glucocorticoid receptor (GR) play an important role in mediating this phenomenon. Additionally, a new direct target gene of GR, Lama5, is identified and confirmed in vivo and in vitro that the corticosterone-GR-LAMA5 axis is a significant pathway mediating chronic psychological stress-induced cardiomyocyte hypertrophy. Moreover, the potential of LAMA5 is validated as a biomarker for myocardial hypertrophy and impaired cardiac function in patients with depression. In summary, a novel hypertrophy-related gene, Lama5 has been identified, that may play an important role in chronic psychological stress-induced cardiomyocyte hypertrophy.

摘要

慢性心理应激与心肌疾病密切相关，但其病理过程和相关机制尚不清楚。在本研究中，进行了5批次动物实验以揭示慢性心理应激对心脏的病理过程，发现心肌细胞肥大是心脏损伤的早期表现。此外，发现皮质酮和糖皮质激素受体（GR）在介导这一现象中起重要作用。另外，鉴定出GR的一个新的直接靶基因Lama5，并在体内和体外证实皮质酮-GR-LAMA5轴是介导慢性心理应激诱导的心肌细胞肥大的重要途径。此外，验证了Lama5作为抑郁症患者心肌肥大和心功能受损生物标志物的潜力。总之，已鉴定出一个新的肥大相关基因Lama5，其可能在慢性心理应激诱导的心肌细胞肥大中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/68ec85a2f841/ADVS-12-e14659-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/c01eb10b5334/ADVS-12-e14659-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/37f0b80811fc/ADVS-12-e14659-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/1019d3f54f1d/ADVS-12-e14659-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/12f38c299b6b/ADVS-12-e14659-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/faccf58ba730/ADVS-12-e14659-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/b89df2fc41e5/ADVS-12-e14659-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/37698630d83c/ADVS-12-e14659-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/57dd65d24947/ADVS-12-e14659-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/68ec85a2f841/ADVS-12-e14659-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/c01eb10b5334/ADVS-12-e14659-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/37f0b80811fc/ADVS-12-e14659-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/1019d3f54f1d/ADVS-12-e14659-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/12f38c299b6b/ADVS-12-e14659-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/faccf58ba730/ADVS-12-e14659-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/b89df2fc41e5/ADVS-12-e14659-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/37698630d83c/ADVS-12-e14659-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/57dd65d24947/ADVS-12-e14659-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3635/12463095/68ec85a2f841/ADVS-12-e14659-g003.jpg

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