Overexpression of insulin-like growth factor-1 in the heart is coupled with myocyte proliferation in transgenic mice.
Transgenic mice were generated in which the cDNA for the human insulin-like growth factor 1B (IGF-1B) was placed under the control of a rat alpha-myosin heavy chain promoter. In mice heterozygous for the transgene, IGF-1B mRNA was not detectable in the fetal heart at the end of gestation, was present in modest levels at 1 day after birth, and increased progressively with postnatal maturation, reaching a peak at 75 days. Myocytes isolated from transgenic mice secreted 1.15 +/- 0.25 ng of IGF-1 per 10(6) cells per 24 hr versus 0.27 +/- 0.10 ng in myocytes from homozygous wild-type littermates. The plasma level of IGF-1 increased 84% in transgenic mice. Heart weight was comparable in wild-type littermates and transgenic mice up to 45 days of age, but a 42%, 45%, 62%, and 51% increase was found at 75, 135, 210, and 300 days, respectively, after birth. At 45, 75, and 210 days, the number of myocytes in the heart was 21%, 31%, and 55% higher, respectively, in transgenic animals. In contrast, myocyte cell volume was comparable in transgenic and control mice at all ages. In conclusion, overexpression of IGF-1 in myocytes leads to cardiomegaly mediated by an increased number of cells in the heart.
Reiss
K
K
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Cheng
W
W
Ferber
A
A
Kajstura
J
J
Li
P
P
Li
B
B
Olivetti
G
G
Homcy
C J
CJ
Baserga
R
R
Anversa
P
P
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology; D006439:Hemodynamics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D009218:Myosins / Q000235:genetics; D009929:Organ Size; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D017931:DNA Primers; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D004247:DNA; D009218:Myosins