Increased insulin-like growth factor-I gene expression precedes left ventricular cardiomyocyte hypertrophy in a rapidly-hypertrophying rat model system.
Chronic pressure overload leads to an increase in the size, i.e. hypertrophy, of cardiomyocytes in the heart. However, the molecular mechanisms underlying this hypertrophy are not understood. Insulin-like growth factor-I (IGF-I) synthesized locally in the heart is known to be associated with the hypertrophic process. So far, however, cardiac IGF-I gene expression in the widely used rat model system has only been shown to be increased when the hypertrophy induced by pressure-overload was already established. Therefore, the question of whether IGF-I serves as an initiating or early-enhancing factor for the cardiac hypertrophy remains unanswered. Here, cardiac hypertension and hypertrophy were rapidly induced in the rat by complete constriction of the abdominal aorta between the origins of the renal arteries. Carotid arterial systolic blood pressure remained unchanged in sham rats but increased rapidly in the pressure-overloaded constricted rats with a sustained hypertension established by 3 days. Hypertrophy of left ventricular (LV) cardiomyocytes in constricted rats also occurred by 3 days. However, this hypertrophy was preceded by increases in LV IGF-I mRNA and protein which occurred within 1 day. These results support the hypothesis that cardiac-synthesized IGF-I is an initiating or early-enhancing factor for hypertrophy of LV cardiomyocytes.
Huang
Chi-Yang
CY
Department of Molecular and Integrative Physiology, University of Illinois, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, IL 61801, USA.
Buchanan
David L
DL
Gordon
Robert L
RL
Sherman
Matthew J
MJ
Razzaq
Jamil
J
White
Karen
K
Buetow
Dennis E
DE
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight; D005786:Gene Expression Regulation; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007118:Immunoassay; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I