INSULIN-LIKE GROWTH-FACTOR-I IS INVOLVED IN INFLAMMATION LINKED ANGIOGENIC PROCESSES AFTER MICROEMBOLISATION IN PORCINE HEART

Objective: Angiogenesis in the porcine heart can be induced by myocard ial ischaemia following vascular occlusions. This process is character ised by increased numbers of monocytes/macrophages, known to be potent producers of various mitogens such as insulin-like growth factors (IG F) and interleukins (IL). The aim of the study was to examine gene exp ression of these factors by means of northern blot hybridisation, slot blot analysis, and in situ hybridisation in a porcine model of corona ry angiogenesis. Methods: Experimental ischaemia and subsequent focal necroses were induced by selective injection of 25 mu m microspheres i nto the left circumflex artery. The hearts were excised after 3-168 h of microembolisation, and tissue was collected from a non-ischaemic co ntrol area and the circumflex region of the same heart for further ana lysis. Results: IGF-I was constitutively transcribed in normal porcine myocardium mainly by myocytes. Following microembolisation, IGF-I mRN A expression was significantly increased in the experimental region (1 .8-fold) after 72 h and to a lesser extent after 168 h. In the ischaem ic region, characterised by capillary sprouting, numerous mononuclear cells contained IGF-I mRNA. In contrast, IGF-II mRNA levels, constitut ively produced by porcine myocytes, were not altered by microembolisat ion. IL-1 alpha, IL-1 beta, and IL-4 mRNA expression was undetectable in our animal model, whereas IL-6 was constitutively transcribed in no rmal and ischaemic heart and remained insensitive to microembolisation and focal necrosis. Conclusion: After microembolisation, increased IG F-I mRNA expression occurred by infiltrating monocytes in areas of mic rosphere induced focal necrosis, where capillary sprouting can be dete cted, suggesting that IGF-I is involved in inflammation linked angioge nic processes.