The somatostatin analog, octreotide, inhibits in vitro outgrowth of smooth muscle cells from canine coronary and carotid atherosclerotic plaque tissues.
Restenosis is caused by excessive neointima formation resulting from smooth muscle cell (SMC) proliferation and migration from the arterial media into the subendothelial space, stimulated by growth factors. A long-acting somatostatin analog, octreotide, activates protein tyrosine phosphatases and can inhibit the stimulatory effects of growth factors. In this study, we evaluated the effect of octreotide on SMC outgrowth from in vitro explants of both coronary and carotid arterial tissues in a canine endothelium-injury model. After 6 days of culture, SMC grew out of 33.3% and 58.3% of the explants from the injured canine carotid and coronary arterial tissues, respectively. In contrast, SMC outgrowth was not observed from any of the explants from normal canine carotid arterial tissue. Octreotide completely inhibited SMC outgrowth from injured canine carotid arterial tissue at a concentration of 10(-6) M. This agent also inhibited SMC outgrowth from injured canine coronary arterial tissue by 57% and 71% of the control value at concentrations of 10(-8) M and 10(-6) M, respectively. We conclude that our explant cell-culture model may prove to be valuable for assessing the effect of agents designed to reduce intimal proliferation, and that the use of the somatostatin analog octreotide in clinical settings may modify the high incidence of restenosis after coronary interventions by reducing SMC proliferation.
Sakamoto
H
H
Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan. sakamoth@news.sb.gunma-u.ac.jp
Sakamaki
T
T
Kanda
T
T
Ito
Y
Y
Sumino
H
H
Masuda
H
H
Ohyama
Y
Y
Ono
Z
Z
Kurabayashi
M
M
Kobayashi
I
I
Nagai
R
R
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology*; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000473:pathology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D015282:Octreotide / Q000494:pharmacology*
D015282:Octreotide