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Upregulation of IGF 1 , IGF 1 ‐receptor, and late growth related genes in ventricular myocytes acutely after infarction in rats
Author(s) -
Reiss Krzysztof,
Meggs Leonard G.,
Li Peng,
Olivetti Giorgio,
Capasso Joseph M.,
Anversa Piero
Publication year - 1994
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041580120
Subject(s) - myocyte , downregulation and upregulation , biology , proliferating cell nuclear antigen , medicine , endocrinology , insulin like growth factor , gene expression , growth factor , receptor , microbiology and biotechnology , gene , immunohistochemistry , biochemistry
To determine the effects of acute myocardial infarction on the expression of insulin‐like growth factor 1 (IGF 1 ) and insulin‐like growth factor 1 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, IGF 1 mRNA increased 4.3‐fold and 9.4‐fold in left and right myocytes, respectively. In order to establish whether the upregulation of IGF 1 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‐H 3 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‐H 3 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 IGF 1 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. © 1994 Wiley‐Liss, Inc.