Alterations in cultured myocardial fibroblast function following the development of left ventricular failure
Alterations in cultured myocardial fibroblast function following the development of left ventricular failure
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DOI：
10.1016/j.yjmcc.2006.01.019
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发表时间：
2006-04-01
影响因子：
5
通讯作者：
Spinale, FG
中科院分区：
文献类型：
--
作者：
Flack, EC;Lindsey, ML;Spinale, FG
心肌细胞外基质（ECM）重构是左心室（LV）衰竭进展过程中的一个结构性事件。心肌成纤维细胞是影响ECM的主要细胞类型，但心肌成纤维细胞中的特定表型差异是否以及在何种程度上可以证明在培养中发生LV衰竭仍不清楚。成年猪（25 kg）用于对照心肌成纤维细胞制备（N=5）或起搏诱导LV衰竭后（N=5; 240 bpm，3周）。左心室舒张末期容积增加证明起搏可发生左心室重构（132 +/- 11 vs.对照组60 +/- 4 mL; P < 0.05）。功能参数，包括迁移，粘附，胶原蛋白和基质金属蛋白酶的释放进行了评估，从第1-4代成纤维细胞培养。以下结果与每次传代一致，并在对照值设定为100%的情况下分析结果。左室衰竭成纤维细胞迁移增加170%以上（P < 0.05）。LV衰竭成纤维细胞与胶原1、层粘连蛋白和纤连蛋白的粘附增加了160%以上（P < 0.05）。在LV衰竭成纤维细胞中，β 1整合素密度降低50%（P < 0.05）。左室衰竭成纤维细胞胶原释放增加130%以上，基质金属蛋白酶-2增加140%（P < 0.05）。这项研究的独特发现是双重的。首先，在体内病理刺激后，成人心肌成纤维细胞通过体内早期传代保持一致的表型。第二，在LV衰竭成纤维细胞中发生ECM组分的差异释放和反应。因此，心肌成纤维细胞的表型转化随着LV衰竭的发展而发生，这反过来可能有助于基质重塑，并作为潜在的细胞治疗靶点。(c)2006爱思唯尔有限公司保留所有权利。
A structural event in the progression of left ventricular (LV) failure is myocardial extracellular matrix (ECM) remodeling. The myocardial fibroblast is a major cell type influencing the ECM, but whether and to what degree specific phenotypic differences in myocardial fibroblasts can be demonstrated to occur in culture with the development of LV failure remains unclear. Adult pigs (25 kg) were used for control myocardial fibroblast preparations (N=5) or following pacing-induced LV failure (N=5; 240 bpm, 3 weeks). LV remodeling occurred with pacing as evidenced by increased LV end diastolic volume (132 +/- 11 vs. 60 +/- 4 mL for control; P < 0.05). Functional parameters including migration, adhesion, collagen and matrix metalloproteinase release were assessed in fibroblast cultures from passages 1-4. The following findings were consistent with each passage and the results were analyzed with control values set to 100%. Migration of LV failure fibroblasts increased by over 170% (P < 0.05). Adhesion to collagen 1, laminin and fibronectin was increased by over 160% in LV failure fibroblasts (P < 0.05). beta(1) integrin density decreased by 50% in LV failure fibroblasts (P < 0.05). Fibrillar collagen release increased by over 130% and matrix metalloproteinase-2 increased by 140% in LV failure fibroblasts (P < 0.05). The unique findings of this study are two-fold. First, after a pathological stimulus in-vivo, adult myocardial fibroblasts maintain a consistent phenotype through early passages in-vivo. Second, a differential release of, and response to ECM components occurred in LV failure fibroblasts. Thus, a phenotypic transformation of the myocardial fibroblast occurs with the development of LV failure, which in turn may contribute to matrix remodeling and presents as a potential cellular therapeutic target. (c) 2006 Elsevier Ltd. All rights reserved.