Changes in IGFs in cardiac tissue following myocardial infarction
Changes in IGFs in cardiac tissue following myocardial infarction
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DOI：
10.1677/joe.0.1630433
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发表时间：
1999-12-01
影响因子：
4
通讯作者：
Bass, JJ
中科院分区：
文献类型：
--
作者：
Matthews, KG;Devlin, GP;Bass, JJ
我们研究了绵羊心肌梗死（MI）模型中IGF轴的变化，以确定梗死后心肌的时间变化与IGF水平之间的关系。免疫细胞化学研究IGF的定位，原位杂交研究IGF的产生，放射配体研究IGF的特异性结合。在存活组织中，IGF-I肽定位于心肌细胞，在梗死后1和2天，毗邻梗死的直接边界区域的免疫染色最强，IGF-I mRNA也增加，在2天达到最大值。存活组织中放射性标记的igf - 1的结合最初低于对照心肌中心肌细胞的结合，随后在梗死后6天显著增加。在坏死组织中，igf - 1肽在梗死后0.5天仍可在心肌细胞中检测到，但在梗死后1天已从该区域清除，在梗死后6天在浸润修复区的巨噬细胞和成纤维细胞中再次检测到。当探针与巨噬细胞和成纤维细胞杂交6天后，坏死组织中才检测到IGF-I mRNA。在坏死区域内，在靠近边界的活组织岛的心肌细胞中观察到高水平的放射性标记的IGF-I与受体和结合蛋白的结合。存活组织心肌细胞IGF-II免疫染色较弱。存活区和坏死区均未检测到IGF-II mRNA。放射性标记的IGF-II主要与存活区域和梗死区域的巨噬细胞结合，尽管与IGF-I一样，在坏死区域边界附近的活组织岛中观察到放射性标记的IGF-II与受体和结合蛋白的高水平结合。我们得出结论，心肌梗死后，梗死边界存活的心肌细胞在IGF- i的定位、产生和特异性结合方面表现出明显的变化，这表明IGF轴直接参与梗死后事件，可能通过诱导心肌肥大来维持心功能，并通过减少凋亡细胞死亡来维持细胞存活，这在其他细胞类型中也得到了证实。
We have studied changes in the IGF axis in an ovine model of myocardial infarction (MI), in order to determine the relationship between time-based changes in post-infarct myocardium and IGF levels. IGF localization was studied by immunocytochemistry, production by in situ hybridization, and specific binding by radioligand studies.In surviving tissue, IGF-I peptide localized to cardiomyocytes, with strongest immunostaining at 1 and 2 days post-infarct in the immediate border area adjoining the infarct, where IGF-I mRNA also increased, reaching a maximum at 2 days. Binding of radiolabelled IGF-I in surviving tissue was initially lower than that seen in cardiomyocytes in control myocardium, subsequently increasing to become significantly greater by 6 days post-infarct.In necrotic tissue, IGF-I peptide was still detectable in cardiomyocytes at 0.5 days post-infarct, but had cleared From this area by 1 day, becoming detectable again at 6 days post-infarct in macrophages and fibroblasts infiltrating the repair zone. IGF-I mRNA was not detected in necrotic tissue until 6 days, when probe hybridized to macrophages and fibroblasts. Within the necrotic zone, high levels of radiolabelled IGF-I binding to a combination of receptors and binding proteins were observed in cardiomyocytes in islands of viable tissue located close to the border.Weak immunostaining for IGF-II was observed in cardiomyocytes of the surviving tissue. IGF-II mRNA was not detected in either surviving or necrotic areas. Binding of radiolabelled IGF-II was predominantly to macrophages in both surviving and infarct areas, although as with IGF-I, high levels of binding of radiolabelled IGF-II to a combination of receptors and binding proteins were observed in islands of viable tissue close to the border within the necrotic area.We conclude that, following MI, surviving cardiomyocytes at the infarct border show marked changes in IGF-I localization, production, and specific binding, indicating that the IGF axis is directly involved in post-infarct events, possibly in the maintenance of cardiac function by the induction of hypertrophy and in cell survival by decreasing apoptotic cell death, which has been demonstrated in other cell types.