人心力衰竭时线粒体、脂滴及肌浆网附着的超微结构分析

IF 2.2
Nadina R. Latchman , Tyler L. Stevens , Kenneth C. Bedi , Benjamin L. Prosser , Kenneth B. Margulies , John W. Elrod
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引用次数: 0

摘要

背景心肌细胞结构重塑被认为是心力衰竭(HF)发生和发展的一个原因。越来越多的证据强调了细胞器在心肌细胞功能和稳态中的作用。细胞器串扰的破坏,如肌浆网(SR)和线粒体之间的串扰,会导致许多细胞过程失调,包括钙处理和细胞生物能量学,这两个过程被破坏并与心脏病理生理有关。虽然细胞器之间的物理距离被认为对稳态心肌细胞功能至关重要,但在人类心力衰竭中,细胞器的相互作用和偶联是否发生了改变尚不清楚。方法在此,我们利用透射电子显微镜来表征各种病因的心衰患者心肌细胞中细胞器附着的作用。随后,我们采用分子方法检测细胞器系链的表达变化。结果我们证明,扩张型心肌病、肥厚型心肌病和缺血性心肌病心脏的心肌细胞与非衰竭对照组相比,线粒体更小、更圆。衰竭的心肌细胞也表现出中断的sr -线粒体并置和各种分子链表达的变化。进一步的分析揭示了脂滴动力学的改变,包括脂滴数量的减少和与衰竭心肌细胞线粒体相关的脂滴减少。结论我们观察到细胞器动力学异常在各种心力衰竭病因中都是保守的。我们的研究结果表明,细胞器结构和对立可能是人类HF进展的一个因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure

Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure

Background

Cardiomyocyte structural remodeling is reported as a causal contributor to heart failure (HF) development and progression. Growing evidence highlights the role of organelle apposition in cardiomyocyte function and homeostasis. Disruptions in organelle crosstalk, such as that between the sarcoplasmic reticulum (SR) and mitochondria, dysregulate numerous cellular processes that include calcium handling and cellular bioenergetics, two processes that are disrupted and implicated in cardiac pathophysiology. While the physical distance between organelles is thought to be essential for homeostatic cardiomyocyte function, whether the interactions and coupling of organelles are altered in human heart failure remains unclear.

Methods

Here, we utilized transmission electron microscopy to characterize the role of organelle apposition in cardiomyocytes from patients with various etiologies of HF. Subsequently, we employed molecular approaches to examine expression changes of proposed organelle tethers.

Results

We demonstrate that cardiomyocytes from dilated cardiomyopathy, hypertrophic cardiomyopathy and ischemic cardiomyopathy hearts display smaller, rounded mitochondria as compared to nonfailing controls. Failing cardiomyocytes also exhibited disrupted SR-mitochondria juxtaposition and changes in the expression of various proposed molecular tethers. Further analysis revealed alterations in lipid droplet dynamics including decreased lipid droplet number and less lipid droplets in association with mitochondria in failing cardiomyocytes.

Conclusion

We observed dysregulated organelle dynamics which was conserved across various etiologies of heart failure. Our results suggest that organelle structure and apposition is a possible contributor to human HF progression.
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来源期刊
Journal of molecular and cellular cardiology plus
Journal of molecular and cellular cardiology plus Cardiology and Cardiovascular Medicine
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