Insulin-like growth factor II is an experimental stress inducible gene in a porcine model of brief coronary occlusions.
OBJECTIVE
Previous observations have shown that myocardium activates many adaptive processes after brief ischaemia. The aim of this study was to determine whether insulin-like growth factors (IGF) as well as their receptors and binding proteins (IGFBP), which control the activity of the IGF, may play an important role during these processes.


METHODS
Ischaemia was induced in anaesthetised open chest pigs by two 10 min occlusions of the left anterior descending coronary artery, separated by 30 min of reperfusion, and followed by reperfusion up to 210 min. Tissue from the ischaemic area and from a non-ischaemic control region of the same heart was examined by means of northern blot, slot blot, and in situ hybridisation.


RESULTS
IGF-I, IGF-II, the type I receptor, the insulin receptor, and IGFBP-2-6 are constitutively expressed in porcine myocardium. In situ hybridisation showed that IGF-I and IGF-II are mainly transcribed by myocytes. Ischaemia/reperfusion led to an early and significant increase in IGF-II mRNA compared to non-sham controls but not in comparison with sham operated animals, which already showed a (not significantly) enhanced IGF-II expression. In each case the IGF-II mRNA levels are equal in the control and the experimental region of the same heart. Whereas IGF-II expression was already increased by experimental stress, IGFBP-5 mRNA was enhanced only by ischaemia/reperfusion. The expression of IGF-I, the receptors, and IGFBP-2, 3, 4, and 6 remained unchanged during the experimental protocol. IGFBP-1 was neither expressed nor induced in our model.


CONCLUSIONS
IGF-II acts like a stress-response gene activated by the experimental conditions (surgery, anaesthesia) and remains induced during following episodes of ischaemia/reperfusion. A possible interaction of IGFBP-5 with other components of the IGF system may contribute to the preconditioning response.
Kluge
A
A
Max-Planck-Institute for Physiological and Clinical Research, Department of Experimental Cardiology, Bad Nauheim, Germany.
Zimmermann
R
R
Münkel
B
B
Verdouw
P D
PD
Schaper
J
J
Schaper
W
W
D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000235:genetics; D017403:In Situ Hybridization; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007511:Ischemia; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine
D002352:Carrier Proteins; D006131:Growth Inhibitors; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II