Investigation of cardiac fibroblasts using myocardial slices.

Investigation of cardiac fibroblasts using myocardial slices.
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DOI:
10.1093/cvr/cvx152
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发表时间:
2018-01-01
影响因子:
10.8
通讯作者:
Terracciano CM
Terracciano CM
中科院分区:
医学1区
文献类型:
--
作者:
Perbellini F;Watson SA;Scigliano M;Alayoubi S;Tkach S;Bardi I;Quaife N;Kane C;Dufton NP;Simon A;Sikkel MB;Faggian G;Randi AM;Gorelik J;Harding SE;Terracciano CM

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心脏成纤维细胞(CF)被认为是心脏纤维化的主要调节因子。影响CF活性的因素很难确定。当在体外分离和培养时,CFs经历快速的表型变化,包括α-SMA表达增加。在这里,我们描述了一个新的模型,研究CFs和他们的反应,药理学和机械刺激,在体外培养的小鼠,狗和人的心肌切片。在培养中,卸载心肌切片诱导CF增殖而不表达α-SMA长达7天。移行到塑料支架上或玻璃培养的CFs在3d内表达αSMA。尽管有转化生长因子-β(20 ng/ml)或血管紧张素II(200 µM)刺激,切片上的细胞仍保持αSMA(−)。当使用A形拉伸器对心肌切片施加舒张负荷时,在第3天和第7天,CF增殖被显著阻止(P < 0.001)。心肌切片允许在多细胞环境中研究CFs,并可用于有效地研究心脏纤维化的机制和潜在靶点。
Cardiac fibroblasts (CFs) are considered the principal regulators of cardiac fibrosis. Factors that influence CF activity are difficult to determine. When isolated and cultured in vitro, CFs undergo rapid phenotypic changes including increased expression of α-SMA. Here we describe a new model to study CFs and their response to pharmacological and mechanical stimuli using in vitro cultured mouse, dog and human myocardial slices. Unloading of myocardial slices induced CF proliferation without α-SMA expression up to 7 days in culture. CFs migrating onto the culture plastic support or cultured on glass expressed αSMA within 3 days. The cells on the slice remained αSMA(−) despite transforming growth factor-β (20 ng/ml) or angiotensin II (200 µM) stimulation. When diastolic load was applied to myocardial slices using A-shaped stretchers, CF proliferation was significantly prevented at Days 3 and 7 (P < 0.001). Myocardial slices allow the study of CFs in a multicellular environment and may be used to effectively study mechanisms of cardiac fibrosis and potential targets.
DOI: 10.1186/1755-1536-5-15
发表时间: 2012-09-03
期刊: Fibrogenesis & tissue repair
影响因子: --
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影响因子: 20.1
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期刊: DEVELOPMENTAL CELL
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