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慢性心力衰竭患者的原发性骨骼肌成肌细胞表现出抗炎和增殖活性丧失。

Primary skeletal muscle myoblasts from chronic heart failure patients exhibit loss of anti-inflammatory and proliferative activity.

作者信息

Sente Tahnee, Van Berendoncks An M, Jonckheere An I, Rodenburg Richard J, Lauwers Patrick, Van Hoof Viviane, Wouters An, Lardon Filip, Hoymans Vicky Y, Vrints Christiaan J

机构信息

Laboratory of Cellular and Molecular Cardiology, Antwerp University Hospital, Edegem, Belgium.

Department of Translational Pathophysiological Research, Cardiovascular Diseases, University of Antwerp, Wilrijk, Belgium.

出版信息

BMC Cardiovasc Disord. 2016 May 26;16:107. doi: 10.1186/s12872-016-0278-3.

Abstract

BACKGROUND

Peripheral skeletal muscle wasting is a common finding with adverse effects in chronic heart failure (HF). Whereas its clinical relevance is beyond doubt, the underlying pathophysiological mechanisms are not yet fully elucidated. We aimed to introduce and characterize the primary culture of skeletal muscle cells from individual HF patients as a supportive model to study this muscle loss.

METHODS AND RESULTS

Primary myoblast and myotubes cultures were successfully propagated from the m. vastus lateralis of 6 HF patients with reduced ejection fraction (HFrEF; LVEF <45 %) and 6 age and gender-matched healthy donors. HFrEF cultures were not different from healthy donors in terms of morphology, such as myoblast size, shape and actin microfilament. Differentiation and fusion indexes were identical between groups. Myoblast proliferation in logarithmic growth phase, however, was attenuated in the HFrEF group (p = 0.032). In addition, HFrEF myoblasts are characterized by a reduced TNFR2 expression and IL-6 secretion (p = 0.017 and p = 0.016; respectively).

CONCLUSION

Biopsy derived primary skeletal muscle myoblasts of HFrEF patients produce similar morphological and myogenic differentiation responses as myoblasts of healthy donors, though demonstrate loss of anti-inflammatory and proliferative activity.

摘要

背景

外周骨骼肌萎缩是慢性心力衰竭(HF)中常见的表现,并具有不良影响。尽管其临床相关性毋庸置疑,但其潜在的病理生理机制尚未完全阐明。我们旨在引入并表征来自个体HF患者的骨骼肌细胞原代培养物,作为研究这种肌肉损失的支持模型。

方法与结果

成功从6例射血分数降低的HF患者(HFrEF;左心室射血分数<45%)以及6例年龄和性别匹配的健康供体的股外侧肌中培养出原代成肌细胞和肌管。HFrEF培养物在形态学方面与健康供体无异,如成肌细胞大小、形状和肌动蛋白微丝。两组之间的分化和融合指数相同。然而,HFrEF组在对数生长期的成肌细胞增殖减弱(p = 0.032)。此外,HFrEF成肌细胞的特征是肿瘤坏死因子受体2(TNFR2)表达降低和白细胞介素-6(IL-6)分泌减少(分别为p = 0.017和p = 0.016)。

结论

源自活检的HFrEF患者原发性骨骼肌成肌细胞产生的形态学和生肌分化反应与健康供体的成肌细胞相似,但抗炎和增殖活性丧失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a5/4880810/d076e7bd4c68/12872_2016_278_Fig1_HTML.jpg

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