UP-REGULATION OF IGF(1), IGF(1)-RECEPTOR, AND LATE GROWTH-RELATED GENES IN VENTRICULAR MYOCYTES ACUTELY AFTER INFARCTION IN RATS

To determine the effects of acute myocardial infarction on the express ion of insulin-like growth factor, (IGF1) and insulin-like growth fact or, receptors (IGF-1R) on the surviving myocytes of the left and right ventricles, large infarcts were produced in rats and the animals sacr ificed 2 days later. Hemodynamic measurements of left and right ventri cular pressures, +dP/dt and -dP/dt, and central venous pressure docume nted that coronary occlusion was associated with a severe impairment o f cardiac function. By employing reverse transcriptase polymerase chai n reaction (RTPCR), a low level of expression of IGF-1R mRNA was detec ted in myocytes from sham-operated rats. Acute myocardial infarction w as found to enhance by nearly twofold the message for IGF-1R in viable myocytes biventricularly. Moreover, IGF1 mRNA increased 4.3-fold and 9.4-fold in left and right myocytes, respectively. In order to establi sh whether the upregulation of IGF1 and IGF-1R with infarction was cou pled with induction of late growth related genes, which are known to b e implicated in DNA replication and mitotic division, proliferating ce ll nuclear antigen (PCNA) and histone-H-3 expression was assessed by N orthern blot and RTPCR. The level of expression of PCNA mRNA was found to be increased 3.9-fold and 2.4-fold in left and right myocytes, res pectively, from infarcted hearts. Corresponding increments in histone- H-3 mRNA were 25.5-fold and 5.3-fold, respectively. However, PCNA prot ein as detected by immunoperoxidase staining was restricted to a limit ed number of myocyte nuclei adjacent to the necrotic myocardium of the left ventricle. In conclusion, acute myocardial infarction is associa ted with enhanced expression of IGF1 and IGF-IR on stressed myocytes, and this phenomenon may activate genes essential for DNA synthesis, po ssibly affecting myocyte growth. These processes may be fundamental fo r the reconstitution of tissue mass and amelioration of function after infarction.