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 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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kluge
A
A
Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany.
Zimmermann
R
R
Münkel
B
B
Mohri
M
M
Sack
S
S
Schaper
J
J
Schaper
W
W
D000818:Animals; D015152:Blotting, Northern; D004617:Embolism / Q000378:metabolism*; D015870:Gene Expression; D006331:Heart Diseases / Q000378:metabolism*; D017403:In Situ Hybridization; D007249:Inflammation; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine
D015850:Interleukin-6; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II