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Human epicardium-derived cells reinforce cardiac sympathetic innervation.
Journal of Molecular and Cellular Cardiology ( IF 4.9 ) Pub Date : 2020-04-08 , DOI: 10.1016/j.yjmcc.2020.04.006
Yang Ge 1 , Anke M Smits 2 , J Conny van Munsteren 3 , Adriana C Gittenberger-de Groot 4 , Robert E Poelmann 4 , Thomas J van Brakel 4 , Martin J Schalij 4 , Marie-José Goumans 2 , Marco C DeRuiter 3 , Monique R M Jongbloed 1
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RATIONALE After cardiac damage, excessive neurite outgrowth (sympathetic hyperinnervation) can occur, which is related to ventricular arrhythmias/sudden cardiac death. Post-damage reactivation of epicardium causes epicardium-derived cells (EPDCs) to acquire a mesenchymal character, contributing to cardiac regeneration. Whether EPDCs also contribute to cardiac re/hyperinnervation, is unknown. AIM To investigate whether mesenchymal EPDCs influence cardiac sympathetic innervation. METHODS AND RESULTS Sympathetic ganglia were co-cultured with mesenchymal EPDCs and/or myocardium, and neurite outgrowth and sprouting density were assessed. Results showed a significant increase in neurite density and directional (i.e. towards myocardium) outgrowth when ganglia were co-cultured with a combination of EPDCs and myocardium, as compared to cultures with EPDCs or myocardium alone. In absence of myocardium, this outgrowth was not directional. Neurite differentiation of PC12 cells in conditioned medium confirmed these results via a paracrine effect, in accordance with expression of neurotrophic factors in myocardial explants co-cultured with EPDCs. Of interest, EPDCs increased the expression of nerve growth factor (NGF) in cultured, but not in fresh myocardium, possibly due to an "ischemic state" of cultured myocardium, supported by TUNEL and Hif1α expression. Cardiac tissues after myocardial infarction showed robust NGF expression in the infarcted, but not remote area. CONCLUSION Neurite outgrowth and density increases significantly in the presence of EPDCs by a paracrine effect, indicating a new role for EPDCs in the occurrence of sympathetic re/hyperinnervation after cardiac damage.

中文翻译:

人心外膜来源的细胞增强心脏交感神经。

理由心脏损伤后,可能会发生过度的神经突增生(交感神经过度受精),这与室性心律不齐/心脏猝死有关。受损的心外膜再激活会导致心外膜来源的细胞(EPDC)获得间充质,从而促进心脏再生。EPDC是否也有助于心脏再/过度神经支配尚不清楚。目的探讨间充质EPDCs是否影响心脏交感神经。方法和结果将交感神经节与间充质EPDC和/或心肌共培养,并评估神经突的生长和发芽密度。结果显示,当神经节与EPDC和心肌共同培养时,神经突密度和定向(即朝向心肌)的生长显着增加,与仅使用EPDC或心肌的培养相比。在没有心肌的情况下,这种增生不是定向的。根据与EPDC共培养的心肌外植体中神经营养因子的表达,条件培养基中PC12细胞的神经突分化通过旁分泌效应证实了这些结果。令人感兴趣的是,EPDC增加了培养的神经生长因子(NGF)的表达,但未增加新鲜心肌的表达,这可能是由于TUNEL和Hif1α表达所支持的培养心肌的“缺血状态”。心肌梗死后的心脏组织在梗死区域表现出强健的NGF表达,但在偏远地区却没有。结论在存在EPDC的情况下,旁分泌效应使神经突的生长和密度显着增加,
更新日期:2020-04-09
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