Coordinate expression of the insulin-like growth factor system after microembolisation in porcine heart
Coordinate expression of the insulin-like growth factor system after microembolisation in porcine heart
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DOI：
10.1016/s0008-6363(96)00236-2
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发表时间：
1997-02-01
影响因子：
10.8
通讯作者：
Schaper, W
中科院分区：
文献类型：
--
作者：
Kluge, A;Zimmermann, R;Schaper, W
目的：猪心冠状动脉微栓塞术在局灶性坏死导致的无菌炎症模型中诱导血管生成。我们最近在这个模型中表明，胰岛素样生长因子I（IGF-I）参与炎症相关的血管生成过程，由于其增强转录缺血72小时后，微球诱导的局灶性坏死，毛细血管发芽，可以检测到浸润单核细胞。为了进一步了解这一过程，我们研究了通过北方印迹分析和原位杂交的基因表达的其他成员的IGF家族，即六个IGF结合蛋白（IGFBPs），胰岛素受体，和I型IGF受体。研究方法：通过将25 μ m非放射性微球注射到猪的左旋支动脉（LCx）中诱导心肌损伤，这些猪在微栓塞3-24、72或168小时后被杀死。从同一心脏的非缺血对照区域和LCx区域收集组织用于进一步分析。结果如下：我们发现缺血组织中的IGFBP-5 mRNA浓度在微栓塞72小时后与来自同一心脏的对照组织相比降低（2.7倍; P < 0.02），之前在3-24小时IGFBP-3 mRNA水平升高1.9倍（P < 0.05）。在所有研究时间点，缺血组织中IGFBP-6均升高。原位杂交结果表明，心肌细胞是IGFBP-3和IGFBP-6 mRNA的主要生产者。IGFBP-2、IGFBP-4、胰岛素受体和I型IGF受体的mRNA水平组成性表达，但在微栓塞后未发生变化。在心脏和其他研究器官中均未检测到IGFBP-1的转录本。此外，我们还证明了IGF系统其他成分的mRNA在除肝脏外的几乎所有猪器官中表达，结论：这些结果表明微栓塞猪心肌中IGF系统的基因协调表达，与IGF-I、IGFBP-3、IGFBP-5和IGFBP-6在炎症相关的血管生成和/或修复过程中的作用一致。
Objectives: Coronary microembolisation in the pig heart induces angiogenesis in a model of sterile inflammation due to focal necrosis. We have recently shown in this model that insulin-like growth factor I(IGF-I) is involved in inflammation-linked angiogenic processes due to its enhanced transcription after 72 h of ischaemia by infiltrating monocytes in areas of microsphere-induced focal necrosis where capillary sprouting could be detected. To obtain further insights into this process we studied by means of Northern blot analysis and in situ hybridisation the gene expression of other members of the IGF family, i.e. the six IGF binding proteins (IGFBPs), the insulin receptor, and the type I IGF receptor. Methods: Myocardial injury was induced by injection of 25 mu m non-radioactive microspheres into the left circumflex artery (LCx) in pigs that were killed after 3-24, 72, or 168 h of microembolisation. Tissue was collected from a non-ischaemic control area and the LCx region of the same heart for further analysis. Results: We found decreased IGFBP-5 (2.7-fold; P < 0.02) mRNA concentrations after 72 h of microembolisation in ischaemic tissue versus control tissue from the same heart, preceded by a 1.9-fold elevated level of IGFBP-3 mRNA at 3-24 h (P < 0.05). IGFBP-6 was increased in ischaemic tissue al all time points studied. In situ hybridisation identified myocytes as the main producers of IGFBP-3 and IGFBP-6 mRNA. The mRNA levels of IGFBP-2, IGFBP-4, the insulin receptor, and the type I IGF receptor were constitutively expressed but did not change after microembolisation, Neither in heart nor in other organs studied transcripts of IGFBP-1 could be detected. Furthermore, we demonstrated that mRNA of the other components of the IGF system was expressed in almost all porcine organs except liver, Conclusion: These results indicate a coordinate gene expression of the IGF system in microembolised porcine myocardium, compatible with a role of IGF-I, IGFBP-3, IGFBP-5, and IGFBP-6 in inflammation-linked angiogenesis and/or repair processes.