Type II diabetes promotes a myofibroblast phenotype in cardiac fibroblasts.
Type II diabetes promotes a myofibroblast phenotype in cardiac fibroblasts.
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DOI：
10.1016/j.lfs.2013.01.003
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发表时间：
2013-03-28
期刊：
影响因子：
6.1
通讯作者：
Goldsmith, Edie C.
中科院分区：
文献类型：
--
作者：
Fowlkes, Vennece;Clark, Jessica;Fix, Charity;Law, Brittany A.;Morales, Mary O.;Qiao, Xian;Ako-Asare, Kayla;Goldsmith, Jack G.;Carver, Wayne;Murray, David B.;Goldsmith, Edie C.
心血管疾病是诊断患有II型糖尿病（DM）的个体的主要死亡原因。在糖尿病患者和动物模型中均描述了心脏功能、左心室壁厚度和纤维化的变化;然而，介导基质沉积增加的因素仍不清楚。本研究的目的是评估在II型糖尿病大鼠模型中心脏成纤维细胞功能是否改变。从14周龄Zucker糖尿病和瘦对照（LC）成年雄性大鼠心脏分离心脏成纤维细胞。检查成纤维细胞重塑三维胶原基质的能力，它们在胶原上的粘附、迁移和增殖以及与胶原重塑相关的基因表达的变化。与LC动物的心脏成纤维细胞相比，糖尿病动物的心脏成纤维细胞表现出显著更大的收缩三维胶原基质的能力。增强的收缩行为与糖尿病成纤维细胞增殖的增加以及α-平滑肌肌动蛋白和I型胶原蛋白的表达升高相关，表明糖尿病成纤维细胞转化为肌成纤维细胞表型。心脏纤维化是糖尿病性心肌病的常见并发症，可能导致观察到的与这种疾病相关的心功能障碍。识别和理解成纤维细胞行为的变化，这有助于增加胶原蛋白和其他基质蛋白的沉积，可能会提供新的治疗目标，以减少糖尿病对心脏的破坏性影响。
Cardiovascular disease is the leading cause of death for individuals diagnosed with type II diabetes mellitus (DM). Changes in cardiac function, left ventricular wall thickness and fibrosis have all been described in patients and animal models of diabetes; however, the factors mediating increased matrix deposition remain unclear. The goal of this study was to evaluate whether cardiac fibroblast function is altered in a rat model of type II DM. Cardiac fibroblasts were isolated from 14 week old Zucker diabetic and lean control (LC) adult male rat hearts. Fibroblasts were examined for their ability to remodel 3-dimensional collagen matrices, their adhesion, migration and proliferation on collagen and changes in gene expression associated with collagen remodeling. Cardiac fibroblasts from diabetic animals demonstrated significantly greater ability to contract 3-dimensional collagen matrices compared to cardiac fibroblasts from LC animals. The enhanced contractile behavior was associated with an increase in diabetic fibroblast proliferation and elevated expression of α-smooth muscle actin and type I collagen, suggesting the transformation of diabetic fibroblasts into a myofibroblast phenotype. Cardiac fibrosis is a common complication in diabetic cardiomyopathy which may contribute to the observed cardiac dysfunction associated with this disease. Identifying and understanding the changes in fibroblast behavior which contribute to the increased deposition of collagen and other matrix proteins may provide novel therapeutic targets for reducing the devastating effects of diabetes on the heart.
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DOI：
10.1358/mf.2003.25.2.723680
发表时间：
2003-03-01
影响因子：
--
作者：
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通讯作者：
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DOI：
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发表时间：
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