Localization of insulin-like growth factor I and inhibition of coronary smooth muscle cell growth by somatostatin analogues in human coronary smooth muscle cells. A potential treatment for restenosis?
In this study, we demonstrate, for the first time, the localization of insulin-like growth factor I (IGF-I) in de novo and restenotic human coronary atherectomy plaques by using immunocytochemical techniques. Smooth muscle cells (SMCs) exhibiting the synthetic phenotype contained a statistically significant higher concentration of IGF-I than SMCs of the contractile phenotype or SMCs from normal coronary arteries. In addition, we provide data to suggest that the long-acting somatostatin analogues octreotide and angiopeptin inhibit IGF-I- and basic fibroblast growth factor (b-FGF)- induced human coronary artery SMC proliferation. Platelet-derived growth factor (PDGF)-stimulated cultures were minimally affected by the addition of octreotide but were significantly inhibited by angiopeptin. All three growth factors stimulated SMC migration in a dose-dependent manner. The somatostatin analogues tested had no effect on growth factor-stimulated SMC migration. Our data suggest that by reducing SMC proliferation, somatostatin analogues may have clinical usefulness in reducing the high incidence of restenosis observed after percutaneous transluminal coronary artery interventions.
Grant
M B
MB
Division of Endocrinology, College of Medicine, University of Florida, Gainesville.
Wargovich
T J
TJ
Ellis
E A
EA
Caballero
S
S
Mansour
M
M
Pepine
C J
CJ
D000328:Adult; D015906:Angioplasty, Balloon, Coronary; D002455:Cell Division / Q000187:drug effects; D003251:Constriction, Pathologic / Q000188:drug therapy; D003324:Coronary Artery Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D015282:Octreotide / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012008:Recurrence; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
D009842:Oligopeptides; D010456:Peptides, Cyclic; D010982:Platelet-Derived Growth Factor; C060347:lanreotide; D016222:Fibroblast Growth Factor 2; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D015282:Octreotide