Kluge A, Zimmermann R, Münkel B, Mohri M, Sack S, Schaper J, Schaper W
Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany.
Cardiovasc Res. 1995 Mar;29(3):407-15.
Angiogenesis in the porcine heart can be induced by myocardial ischaemia following vascular occlusions. This process is characterised by increased numbers of monocytes/macrophages, known to be potent producers of various mitogens such as insulin-like growth factors (IGF) and interleukins (IL). The aim of the study was to examine gene expression of these factors by means of northern blot hybridisation, slot blot analysis, and in situ hybridisation in a porcine model of coronary angiogenesis.
Experimental ischaemia and subsequent focal necroses were induced by selective injection of 25 microns microspheres into the left circumflex artery. The hearts were excised after 3-168 h of microembolisation, and tissue was collected from a non-ischaemic control area and the circumflex region of the same heart for further analysis.
IGF-I was constitutively transcribed in normal porcine myocardium mainly by myocytes. Following microembolisation, IGF-I mRNA expression was significantly increased in the experimental region (1.8-fold) after 72 h and to a lesser extent after 168 h. In the ischaemic region, characterised by capillary sprouting, numerous mononuclear cells contained IGF-I mRNA. In contrast, IGF-II mRNA levels, constitutively produced by porcine myocytes, were not altered by microembolisation. IL-1 alpha, IL-1 beta, and IL-4 mRNA expression was undetectable in our animal model, whereas IL-6 was constitutively transcribed in normal and ischaemic heart and remained insensitive to microembolisation and focal necrosis.
After microembolisation, increased IGF-I mRNA expression occurred by infiltrating monocytes in areas of microsphere induced focal necrosis, where capillary sprouting can be detected, suggesting that IGF-I is involved in inflammation linked angiogenic processes.
血管闭塞后心肌缺血可诱导猪心脏血管生成。这一过程的特征是单核细胞/巨噬细胞数量增加，已知这些细胞是多种有丝分裂原的强大生产者，如胰岛素样生长因子（IGF）和白细胞介素（IL）。本研究的目的是通过Northern印迹杂交、斑点印迹分析和原位杂交，在猪冠状动脉血管生成模型中检测这些因子的基因表达。
通过向左旋支动脉选择性注射25微米微球诱导实验性缺血及随后的局灶性坏死。在微栓塞3 - 168小时后切除心脏，从同一心脏的非缺血对照区域和左旋支区域收集组织进行进一步分析。
IGF - I在正常猪心肌中主要由心肌细胞组成性转录。微栓塞后，实验区域IGF - I mRNA表达在72小时后显著增加（1.8倍），168小时后增加程度较小。在以毛细血管芽生为特征的缺血区域，许多单核细胞含有IGF - I mRNA。相比之下，由猪心肌细胞组成性产生的IGF - II mRNA水平不受微栓塞影响。在我们的动物模型中未检测到IL - 1α、IL - 1β和IL - 4 mRNA表达，而IL - 6在正常和缺血心脏中均组成性转录，且对微栓塞和局灶性坏死不敏感。
微栓塞后，在微球诱导的局灶性坏死区域，浸润的单核细胞使IGF - I mRNA表达增加，在该区域可检测到毛细血管芽生，提示IGF - I参与炎症相关的血管生成过程。
