Direct effects of somatostatin analog octreotide on insulin-like growth factor-I in the arterial wall.
Local vascular expression and action of insulin-like growth factor-I (IGF-I) appear to be important in the biologic events that follow arterial wall injury. Octreotide, a long-acting somatostatin analog, is a potent inhibitor of the growth hormone/IGF-I axis. We examined the effects of octreotide on the vascular IGF-I and IGF-binding proteins (IGFBP), gene regulation, smooth muscle cell proliferation, and neointimal thickening after arterial wall injury. Treatment with octreotide selectively decreased IGF-I mRNA expression in normal rat arteries by 70% and prevented the induction of the IGF-I gene after balloon injury. Because up-regulation of platelet-derived growth factor-A gene was not affected, and because there was no change in plasma growth hormone, IGF-I, and glucagon levels, it appears that this effect is selective and mediated locally. Of the IGFBP, IGFBP-4 was modestly up-regulated after balloon injury, whereas treatment with octreotide had no effect on IGFBP-4 expression. The inhibitory effects of octreotide on vascular IGF-I were associated with a decrease in the number of proliferating cell nuclear antigen-positive cells and an up to 90% reduction in neointimal thickening after balloon injury in a dose-dependent fashion.
Yumi
K
K
Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California 90048-0750, USA.
Fagin
J A
JA
Yamashita
M
M
Fishbein
M C
MC
Shah
P K
PK
Kaul
S
S
Niu
W
W
Nilsson
J
J
Cercek
B
B
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005934:Glucagon / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015282:Octreotide / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects*
D018809:Proliferating Cell Nuclear Antigen; D007334:Insulin-Like Growth Factor I; D005934:Glucagon; D015282:Octreotide