Acute myocardial infarction leads to upregulation of the IGF-1 autocrine system, DNA replication, and nuclear mitotic division in the remaining viable cardiac myocytes.
Insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) are required for cell proliferation in vitro, raising the possibility that an autocrine IGF-1-IGF-1R system may be present in vivo and become activated in the viable ventricular myocytes shortly after infarction. Therefore, following the in vivo documentation of left ventricular failure in rats subjected to occlusion of the left coronary artery, the unaffected myocytes of the left ventricle were enzymatically dissociated and the expression of IGF-1R and IGF-1 mRNAs were measured at 12 h and at 1, 2-3, and 7 days after surgery. The level of expression of IGF-1R mRNA increased at 12 h and remained elevated at 1 and 2-3 days following coronary ligation. In addition, an increased level of IGF-1R protein on these cells was found. This phenomenon was coupled with the enhanced expression of IGF-1 mRNA in the muscle cells at all intervals. Myocardial infarction was also accompanied by an upregulation of proliferating cell nuclear antigen (PCNA) mRNA in myocytes and the detection of PCNA protein in nearly 1% of the cells. Similarly, bromodeoxyuridine labeling demonstrated that a comparable number of myocytes was positively stained. Finally, mitotic images in myocytes were observed. Thus, the IGF-1R-IGF-1 autocrine system may modulate myocyte cellular hyperplasia in the failing heart.
Reiss
K
K
Department of Medicine, New York Medical College, Valhalla 10595.
Kajstura
J
J
Zhang
X
X
Li
P
P
Szoke
E
E
Olivetti
G
G
Anversa
P
P
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D004247:DNA; D004261:DNA Replication; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015854:Up-Regulation
D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D007334:Insulin-Like Growth Factor I; D004247:DNA; D017526:Receptor, IGF Type 1