慢性间歇性缺氧引发心脏纤维化:附睾白色脂肪组织衰老重塑的作用?

IF 5.6 2区 医学 Q1 PHYSIOLOGY
Suzain Naushad, Jonathan Gaucher, Zaineb Mezdari, Maximin Détrait, Elise Belaidi, Yanyan Zhang, Guillaume Vial, Sophie Bouyon, Gabor Czibik, Maria Pini, Sahar Aldekwer, Hao Liang, Véronique Pelloux, Judith Aron-Wisnewsky, Renaud Tamisier, Jean-Louis Pépin, Geneviève Derumeaux, Daigo Sawaki, Claire Arnaud
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引用次数: 0

摘要

目的阻塞性睡眠呼吸暂停(OSA)是一个日益严重的健康问题,影响着全球近 10 亿人。OSA 的主要特征是慢性间歇性缺氧 (CIH),导致包括心脏病在内的多种器官损伤。慢性间歇性缺氧会严重改变内脏白色脂肪组织(WAT)和心脏的结构与功能,但人们对慢性间歇性缺氧背景下器官间的相互作用知之甚少。我们最近的研究表明,内脏白脂肪组织的衰老驱动了无 CIH 的老年小鼠心肌的改变。方法在第一个实验中,10 周大的 C57bl6J 雄性小鼠(n = 10/组)暴露于 14 天的 CIH(每天 8 小时,5%-21% 的循环吸氧分数,每个循环 60 秒)。在第二个系列中,小鼠在暴露于 CIH 前接受附睾 WAT 手术切除术或假手术。最后,我们使用了 p53 缺陷小鼠或野生型(WT)同窝小鼠,它们也暴露于相同的 CIH 方案。结果CIH诱导的附睾WAT重塑以纤维化、氧化应激、DNA损伤反应、炎症和衰老标记物(p16、p21和p53)表达增加为特征。CIH诱导的附睾WAT重塑与微妙的早期心肌间质纤维化有关。结论短期暴露于CIH诱导附睾WAT衰老重塑和心肌间质纤维化,切除附睾WAT可防止后者的发生。这一发现有力地表明,内脏WAT衰老是缓解OSA相关心脏疾病的一个新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Chronic intermittent hypoxia triggers cardiac fibrosis: Role of epididymal white adipose tissue senescent remodeling?

Chronic intermittent hypoxia triggers cardiac fibrosis: Role of epididymal white adipose tissue senescent remodeling?

Aim

Obstructive sleep apnea (OSA) is a growing health problem affecting nearly 1 billion people worldwide. The landmark feature of OSA is chronic intermittent hypoxia (CIH), accounting for multiple organ damage, including heart disease. CIH profoundly alters both visceral white adipose tissue (WAT) and heart structure and function, but little is known regarding inter-organ interaction in the context of CIH. We recently showed that visceral WAT senescence drives myocardial alterations in aged mice without CIH. Here, we aimed at investigating whether CIH induces a premature visceral WAT senescent phenotype, triggering subsequent cardiac remodeling.

Methods

In a first experiment, 10-week-old C57bl6J male mice (n = 10/group) were exposed to 14 days of CIH (8 h daily, 5%–21% cyclic inspired oxygen fraction, 60 s per cycle). In a second series, mice were submitted to either epididymal WAT surgical lipectomy or sham surgery before CIH exposure. Finally, we used p53 deficient mice or Wild-type (WT) littermates, also exposed to the same CIH protocol. Epididymal WAT was assessed for fibrosis, DNA damages, oxidative stress, markers of senescence (p16, p21, and p53), and inflammation by RT-qPCR and histology, and myocardium was assessed for fibrosis and cardiomyocyte hypertrophy.

Results

CIH-induced epididymal WAT remodeling characterized by increased fibrosis, oxidative stress, DNA damage response, inflammation, and increased expression of senescent markers. CIH-induced epididymal WAT remodeling was associated with subtle and early myocardial interstitial fibrosis. Both epididymal WAT surgical lipectomy and p53 deletion prevented CIH-induced myocardial fibrosis.

Conclusion

Short-term exposure to CIH induces epididymal WAT senescent remodeling and cardiac interstitial fibrosis, the latter being prevented by lipectomy. This finding strongly suggests visceral WAT senescence as a new target to mitigate OSA-related cardiac disorders.

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来源期刊
Acta Physiologica
Acta Physiologica 医学-生理学
CiteScore
11.80
自引率
15.90%
发文量
182
审稿时长
4-8 weeks
期刊介绍: Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.
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