TGF-β1过表达:老年人舒张充盈功能障碍的一种机制

D. Larson, R. Ingham, Cory M. Alwardt, Bo Yang
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引用次数: 2

摘要

在美国,心血管疾病的患病率随着年龄的增长而急剧上升。衰老心肌的一个显著特征是纤维化增加导致舒张功能障碍。此外,心肌梗死后患者的生存与年龄呈负相关,这在一定程度上是由于心肌成纤维细胞介导的不适应重构所致。我们的假设是,心肌成纤维细胞(CF)功能障碍导致TGF-β1过表达,导致老年人群心脏胶原蛋白含量增加。TGF-β1刺激心肌组织中胶原蛋白等细胞外基质蛋白的合成。RT-PCR分析老年小鼠CF TGF-β1 mRNA表达量较年轻小鼠增加43%。左心室的刚度用舒张末期压力-容积关系参数(mmHg/L)的斜率表示。在小鼠模型中,我们证明了年轻小鼠为0.30±0.05,而老年小鼠为0.52±0.10 (p < 0.05)。心室僵硬度与心肌胶原含量相关;即,年轻人和老年人的总蛋白含量分别为9.5±4.0和16.4±2.3% (p < 0.05)。总之,基因结构-功能关系支持我们的假设,即心脏成纤维细胞失调有助于老年人舒张充盈功能障碍。这些数据提供了舒张功能障碍的潜在机制,这可能对老年心内直视手术患者的护理至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TGF-β1 Overexpression: A Mechanism of Diastolic Filling Dysfunction in the Aged Population
The prevalence of cardiovascular disease in the United States dramatically increases with age. A hallmark feature of the aged myocardium is increased fibrosis resulting in diastolic dysfunction. Moreover, the survival of patients subsequent to a myocardial infarction is inversely related to age because of a certain extent to maladaptive remodeling mediated by cardiac fibroblasts. Our hypothesis is that cardiac fibroblast (CF) dysfunction results in overexpressed TGF-β1 leading to increased cardiac collagen content in the aged population. TGF-β1 stimulates the synthesis of the extracellular matrix proteins, including collagen in the cardiac tissues. The RT–PCR analysis of mRNA expression of TGF-β1 of the CF was increased by 43% in the aged mice as compared to the younger. The stiffness of the left ventricle is expressed with the slope of the end-diastolic pressure-volume relationship parameter, (mmHg/L). In a mouse model, we demonstrated that was 0.30 ± 0.05 in the young as compared to 0.52 ± 0.10 in the aged (p < .05). The ventricular stiffness was associated with the myocardial collagen content; namely, young versus the aged was 9.5 ± 4.0 as compared to 16.4 ± 2.3% of total protein, respectively (p < .05). In conclusion, the gene structure–function relationships support our hypothesis that cardiac fibroblast disregulation contributes to diastolic filling dysfunction in elderly persons. These data provide a potential contributory mechanism for diastolic dysfunction that may be vital in caring for the aged open-heart surgical patient.
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