Local insulin-like growth factor I expression induces physiologic, then pathologic, cardiac hypertrophy in transgenic mice

In the present study we determined the long-term effects of persistent, local insulin-like growth factor I (IGF-I) expression on cardiac function in the SIS2 transgenic mouse. Cardiac mass/tibial length was increased in SIS2 mice by 10 wk of age; this cardiac hypertrophy became more pronounced later...

Full description

Saved in:
Bibliographic Details
Published inThe FASEB journal Vol. 13; no. 14; p. 1923
Main Authors Delaughter, M C, Taffet, G E, Fiorotto, M L, Entman, M L, Schwartz, R J
Format Journal Article
LanguageEnglish
Published United States 01.11.1999
Subjects
Animals
Cardiomegaly - etiology
Humans
Insulin-Like Growth Factor I - genetics
Insulin-Like Growth Factor I - physiology
Mice
Mice, Transgenic
Myocardium - pathology
Systole
Transgenes
Non-programmatic
Online AccessGet more information

Cover

More Information
Summary:In the present study we determined the long-term effects of persistent, local insulin-like growth factor I (IGF-I) expression on cardiac function in the SIS2 transgenic mouse. Cardiac mass/tibial length was increased in SIS2 mice by 10 wk of age; this cardiac hypertrophy became more pronounced later in life. Peak aortic outflow velocity, a correlate of cardiac output, was increased at 10 wk in SIS2 mice but was decreased at 52 wk. 72 wk SIS2 mouse hearts exhibited wide variability in the extent of cardiac hypertrophy and enlargement of individual cardiac myofibers. Sirius red staining revealed increased fibrosis in 72 wk SIS2 hearts. Persistent local IGF-I expression is sufficient to initially induce an analog of physiological cardiac hypertrophy in which peak aortic outflow velocity is increased relative to controls in the absence of any observed detrimental histological changes. However, this hypertrophy progresses to a pathological condition characterized by decreased systolic performance and increased fibrosis. Our results confirm the short-term systolic performance benefit of increased IGF-I, but our demonstration that IGF-I ultimately diminishes systolic performance raises doubt about the therapeutic value of chronic IGF-I administration. Considering these findings, limiting temporal exposure to IGF-I seems the most likely means of delivering IGF-I's potential benefits while avoiding its deleterious side effects.
ISSN:0892-6638
DOI:10.1096/fasebj.13.14.1923