Uptake by vascular smooth muscle cells plays an important role in targeting of lipid microspheres incorporating prostaglandin E1 into a thickened intima.
A study was done to determine how lipid microspheres (LM) containing prostaglandin E1 (lipo PGE1) accumulate in injured arterial tissue. After administration of lipo PGE1 labeled with a fluorescence probe, 1,1'-dioctadecyl-3, 3, 3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-lipo PGE1) to rats 14 of days after balloon injury of the carotid artery, localization into the injured site was examined using a fluorescence confocal laser scanning microscope (CLSM). In contrast with the normal carotid artery, DiI-lipo PGE1 accumulated remarkably in neointima of the injured site which was occupied mainly by the migration of the proliferating and quiescent vascular smooth muscle cells (SMC). In vitro cellular uptake of DiI-lipo PGE1 was semi-quantitatively measured using CLSM, regarding differentiated and proliferative phenotypes of human vascular SMC, compared with the human endothelial cells (EC) and mouse fibroblasts. The differentiated SMC incorporated DiI-lipo PGE1 to equal or a higher level of the proliferative phenotype, and was significantly higher than EC and fibroblasts. The uptake of DiI-lipo PGE1 by both SMC and EC was inhibited at 4 degrees C, by dansylcadaverine and excessive LM, but was unaffected by cytochalasin B. These results suggest that the uptake of DiI-lipo PGE1 by SMC plays an important role in localization of DiI-lipo PGE1 at the injured site, and that the uptake seems to be a receptor mediated endocytosis.
Chino
Y
Y
Research Center, Taisho Pharmaceutical Co., Ltd., Ohmiya, Saitama, Japan. s15958@ccm.taisho.co.jp
Minagawa
T
T
Kohno
Y
Y
Toda
Y
Y
Murakami
S
S
Higuchi
S
S
D016475:3T3 Cells / Q000378:metabolism; D000527:Alprostadil / Q000493:pharmacokinetics*; D000818:Animals; D002103:Cadaverine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002232:Carbocyanines / Q000493:pharmacokinetics; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D003571:Cytochalasin B / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
D002232:Carbocyanines; D005456:Fluorescent Dyes; D008081:Liposomes; D003571:Cytochalasin B; C024286:3,3'-dioctadecylindocarbocyanine; D000527:Alprostadil; C008542:monodansylcadaverine; D002103:Cadaverine