Kluge A, Zimmermann R, Weihrauch D, Mohri M, Sack S, Schaper J, Schaper W
Max Planck Institute for Physiological and Clinical Research, Department of Experimental Cardiology, Bad Nauheim, Germany.
Cardiovasc Res. 1997 Feb;33(2):324-31. doi: 10.1016/s0008-6363(96)00236-2.
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.
Myocardial injury was induced by injection of 25 microns 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.
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 at 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.
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.
在猪心脏中，冠状动脉微栓塞可在无菌性炎症模型中诱导血管生成，该模型由局灶性坏死引起。我们最近在这个模型中发现，胰岛素样生长因子I（IGF-I）参与了与炎症相关的血管生成过程，因为在缺血72小时后，浸润到微球诱导的局灶性坏死区域的单核细胞使其转录增强，在该区域可检测到毛细血管发芽。为了进一步深入了解这一过程，我们通过Northern印迹分析和原位杂交研究了IGF家族其他成员的基因表达，即六种IGF结合蛋白（IGFBPs）、胰岛素受体和I型IGF受体。
通过向猪的左旋冠状动脉（LCx）注射25微米的非放射性微球来诱导心肌损伤，在微栓塞3 - 24小时、72小时或168小时后处死猪。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。
我们发现，与同一心脏的对照组织相比，缺血组织在微栓塞72小时后IGFBP - 5 mRNA浓度降低（2.7倍；P < 0.02），在3 - 24小时时IGFBP - 3 mRNA水平升高1.9倍（P < 0.05）。在所有研究的时间点，缺血组织中的IGFBP - 6均增加。原位杂交确定心肌细胞是IGFBP - 3和IGFBP - 6 mRNA的主要产生者。IGFBP - 2、IGFBP - 4、胰岛素受体和I型IGF受体的mRNA水平呈组成性表达，但在微栓塞后未发生变化。在心脏和其他研究的器官中均未检测到IGFBP - 1的转录本。此外，我们证明除肝脏外，IGF系统的其他成分的mRNA在几乎所有猪器官中均有表达。
这些结果表明IGF系统在微栓塞猪心肌中存在协调的基因表达，这与IGF - I、IGFBP - 3、IGFBP - 5和IGFBP - 6在与炎症相关的血管生成和/或修复过程中的作用相一致。
