title: Myocardial infarction and the myocyte IGF1 autocrine system.
abstract: To determine the effects of acute myocardial infarction on the extent and distribution of mural stress on surviving myocardial tissue, coronary artery occlusion was surgically produced in rats. Following haemodynamic measurements in vivo, the characteristics of cardiac anatomy were determined and found to consist of an increase in mid-chamber lumenal diameter and a decrease in wall thickness. The combination of these phenomena resulted in an eight-fold increase in diastolic wall stress on the remaining viable portion of the wall and severe impairment of left and right ventricular performance. Since insulin-like growth factor-1 (IGF1) and its receptor (IGF1R) are required for cell growth in vitro, the possibility was raised that an autocrine IGF1-IGF1R system may be present in vivo and may become activated in viable ventricular myocytes shortly after infarction. Therefore, the unaffected myocytes of the left ventricle were enzymatically dissociated and the expression of IGF1R and IGF1 mRNAs were measured at 12 h and at 1, 2-3, and 7 days after surgery. The level of IGF1R mRNA increased at 12 h and remained elevated at 1 and 2-3 days following coronary artery ligation. In addition, an increased level of IGF1R protein was found on these cells. This phenomenon was coupled with the enhanced expression of IGF1 mRNA in the muscle cells at all points. Thus, the marked elevation in ventricular loading after coronary occlusion may activate the IGF1-IGF1R autocrine system of the unaffected cells, modulating the cellular growth processes implicated in short-term ventricular remodelling of the infarcted heart.
authors.affiliation: Department of Medicine, New York Medical College, Valhalla 10595, USA.
authors.forename: P
authors.initials: P
authors.lastname: Anversa
authors.forename: K
authors.initials: K
authors.lastname: Reiss
authors.forename: J
authors.initials: J
authors.lastname: Kajstura
authors.forename: W
authors.initials: W
authors.lastname: Cheng
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: E H
authors.initials: EH
authors.lastname: Sonnenblick
authors.forename: G
authors.initials: G
authors.lastname: Olivetti
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000502:physiology; D002306:Cardiac Volume / Q000502:physiology; D006332:Cardiomegaly / Q000473:pathology*; D003971:Diastole / Q000502:physiology; D006333:Heart Failure / Q000473:pathology*; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
chemical_list: D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1