FABP4 可增强脂质和纤维化心脏结构及 Ca2+ 动态变化

IF 9.1 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Circulation. Arrhythmia and electrophysiology Pub Date : 2024-09-01 Epub Date: 2024-08-30 DOI:10.1161/CIRCEP.123.012683
Marinela Couselo-Seijas, Xocas Vázquez-Abuín, María Gómez-Lázaro, Laetitia Pereira, Ana M Gómez, Ricardo Caballero, Eva Delpón, Susana Bravo, José Ramón González-Juanatey, Sonia Eiras
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引用次数: 0

摘要

背景:长期持续性心房颤动患者的心外膜基质中脂肪细胞FABP4(脂肪酸结合蛋白4)增加。由于该分子主要由脂肪细胞释放,我们的目的是研究其在心房心肌病中的作用,重点关注纤维化、新陈代谢和电生理变化。这些结果可能会澄清脂肪作为心房心肌病介质的作用:我们使用了几种临床前细胞模型、接受开胸手术患者的心外膜和皮下基质原代细胞培养物、人心房成纤维细胞、来源于人诱导多能干细胞并从成年小鼠体内分离的心房心肌细胞以及转染 Nav1.5 的中国仓鼠卵巢细胞。通过伤口愈合、酶法、比色法、荧光测定、实时定量聚合酶链反应和 TripleTOF 蛋白组学测定了纤维化、葡萄糖、线粒体和脂肪生成活性、基因表达和蛋白质组学。分子变化通过拉曼共聚焦显微光谱分析,钙动力学通过共聚焦显微镜分析,离子电流通过膜片钳分析。心外膜、皮下、心房成纤维细胞和心肌细胞与浓度为 100 ng/mL 的 FABP4 一起培养:结果:我们的研究结果表明,FABP4 能诱导心外膜、皮下基质细胞和心房成纤维细胞纤维化、糖代谢和脂质积累。此外,它还改变了心房心肌细胞的脂质含量和钙动力学,但对 INa 没有影响:结论:FABP4 对心外膜基质产生纤维化和代谢变化,并改变心房心肌细胞的脂质含量和钙动态。这些结果表明,FABP4 可能是心房心肌病的介质。
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FABP4 Enhances Lipidic and Fibrotic Cardiac Structural and Ca2+ Dynamic Changes.

Background: Adipocyte FABP4 (fatty acid-binding protein 4) is augmented in the epicardial stroma of patients with long-standing persistent atrial fibrillation. Because this molecule is released mainly by adipocytes, our objective was to study its role in atrial cardiomyopathy, focusing our attention on fibrosis, metabolism, and electrophysiological changes. These results might clarify the role of adiposity as a mediator of atrial cardiomyopathy.

Methods: We used several preclinical cellular models, epicardial and subcutaneous stroma primary cell cultures from patients undergoing open heart surgery, human atrial fibroblasts, atrial cardiomyocytes derived from human induced pluripotent stem cells and isolated from adult mice, and Nav1.5 transfected Chinese hamster ovary cells. Fibrosis, glucose, mitochondrial and adipogenesis activity, gene expression, and proteomics were determined by wound healing, enzymatic, colorimetric, fluorescence assays, real-time quantitative polymerase chain reaction, and TripleTOF proteomics. Molecular changes were analyzed by Raman confocal microspectroscopy, calcium dynamics by confocal microscopy, and ion currents by patch clamp. Epicardial, subcutaneous, and atrial fibroblasts and cardiomyocytes were incubated with FABP4 at 100 ng/mL.

Results: Our results showed that FABP4 induced fibrosis, glucose metabolism, and lipid accumulation on epicardial and subcutaneous stroma cells and atrial fibroblasts. Besides, it modified lipid content and calcium dynamics in atrial cardiomyocytes without effects on INa.

Conclusions: FABP4 exerts fibrotic and metabolic changes on epicardial stroma and modifies lipid content and calcium dynamic on atrial cardiomyocytes. These results suggest its possible role as an atrial cardiomyopathy mediator.

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来源期刊
CiteScore
13.70
自引率
4.80%
发文量
187
审稿时长
4-8 weeks
期刊介绍: Circulation: Arrhythmia and Electrophysiology is a journal dedicated to the study and application of clinical cardiac electrophysiology. It covers a wide range of topics including the diagnosis and treatment of cardiac arrhythmias, as well as research in this field. The journal accepts various types of studies, including observational research, clinical trials, epidemiological studies, and advancements in translational research.
期刊最新文献
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