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Type II diabetes promotes a myofibroblast phenotype in cardiac fibroblasts

机译:II型糖尿病可促进心脏成纤维细胞的成纤维细胞表型

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Aims 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. Main methods 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. Key findings 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 ??-smooth muscle actin and type I collagen, suggesting the transformation of diabetic fibroblasts into a myofibroblast phenotype. Significance 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. ? 2013 Elsevier Inc.
机译:目的心血管疾病是诊断为II型糖尿病(DM)的个人的主要死亡原因。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,调解基质沉积增加的因素仍不清楚。这项研究的目的是评估在II型DM大鼠模型中心脏成纤维细胞功能是否改变。主要方法从14周龄的Zucker糖尿病和瘦肉对照(LC)成年雄性大鼠心脏中分离出心脏成纤维细胞。检查成纤维细胞重塑3维胶原蛋白基质的能力,它们在胶原蛋白上的粘附,迁移和增殖以及与胶原蛋白重构相关的基因表达的变化。关键发现与来自LC动物的心脏成纤维细胞相比,来自糖尿病动物的心脏成纤维细胞表现出明显的3维胶原基质收缩能力。收缩行为的增强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有关,表明糖尿病成纤维细胞转化为肌成纤维细胞表型。意义心脏纤维化是糖尿病性心肌病的常见并发症,可能导致与该疾病相关的观察到的心脏功能障碍。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,可能为减少糖尿病对心脏的破坏性作用提供新的治疗靶标。 ? 2013爱思唯尔公司

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