Upregulation of IGF1, IGF1-receptor, and late growth related genes in ventricular myocytes acutely after infarction in rats.
To determine the effects of acute myocardial infarction on the expression of insulin-like growth factor1 (IGF1) and insulin-like growth factor1 receptors (IGF-1R) on the surviving myocytes of the left and right ventricles, large infarcts were produced in rats and the animals sacrificed 2 days later. Hemodynamic measurements of left and right ventricular pressures, +dP/dt and -dP/dt, and central venous pressure documented that coronary occlusion was associated with a severe impairment of cardiac function. By employing reverse transcriptase polymerase chain reaction (RTPCR), a low level of expression of IGF-1R mRNA was detected in myocytes from sham-operated rats. Acute myocardial infarction was 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 establish whether the upregulation of IGF1 and IGF-1R with infarction was coupled with induction of late growth related genes, which are known to be implicated in DNA replication and mitotic division, proliferating cell nuclear antigen (PCNA) and histone-H3 expression was assessed by Northern 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, respectively from infarcted hearts. Corresponding increments in histone-H3 mRNA were 25.5-fold and 5.3-fold, respectively. However, PCNA protein as detected by immunoperoxidase staining was restricted to a limited number of myocyte nuclei adjacent to the necrotic myocardium of the left ventricle. In conclusion, acute myocardial infarction is associated with enhanced expression of IGF1 and IGF-1R on stressed myocytes, and this phenomenon may activate genes essential for DNA synthesis, possibly affecting myocyte growth. These processes may be fundamental for the reconstitution of tissue mass and amelioration of function after infarction.
Reiss
K
K
Department of Medicine, New York Medical College, Valhalla 10595.
Meggs
L G
LG
Li
P
P
Olivetti
G
G
Capasso
J M
JM
Anversa
P
P
D000818:Animals; D001483:Base Sequence; D015870:Gene Expression; D006352:Heart Ventricles; D006657:Histones / Q000235:genetics; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D017451:Receptors, Somatomedin / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism*; D015854:Up-Regulation; D016276:Ventricular Function
D006657:Histones; D015335:Molecular Probes; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D017451:Receptors, Somatomedin; D013002:Somatomedins; D012194:RNA-Directed DNA Polymerase