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Titolo:
SUSTAINED INHIBITION OF INTIMAL THICKENING - IN-VITRO AND IN-VIVO EFFECTS OF POLYMERIC BETA-CYCLODEXTRIN SULFATE
Autore:
BACHINSKY WB; BARNATHAN ES; LIU HY; OKADA SS; KUO A; RAGHUNATH PN; MUTTREJA M; CARON RJ; TOMASZEWSKI JE; WEISZ PB; GOLDEN MA;
Indirizzi:
HOSP UNIV PENN,SILVERSTEIN 4,3400 SPRUCE ST PHILADELPHIA PA 19104 UNIV PENN,SCH MED PHILADELPHIA PA 19104 UNIV PENN,SCH ENGN PHILADELPHIA PA 19104
Titolo Testata:
The Journal of clinical investigation
fascicolo: 6, volume: 96, anno: 1995,
pagine: 2583 - 2592
SICI:
0021-9738(1995)96:6<2583:SIOIT->2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
MUSCLE CELL-PROLIFERATION; FIBROBLAST GROWTH-FACTOR; SMOOTH-MUSCLE; CORONARY ANGIOPLASTY; ENDOTHELIAL INJURY; ARTERIAL INJURY; HEPARIN; RESTENOSIS; INVIVO; TETRADECASULFATE;
Keywords:
ANGIOPLASTY; SMOOTH MUSCLE CELL; RESTENOSIS; FIBROBLAST; GROWTH FACTOR; MIGRATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
W.B. Bachinsky et al., "SUSTAINED INHIBITION OF INTIMAL THICKENING - IN-VITRO AND IN-VIVO EFFECTS OF POLYMERIC BETA-CYCLODEXTRIN SULFATE", The Journal of clinical investigation, 96(6), 1995, pp. 2583-2592

Abstract

Intimal thickening after vascular injury may be modulated in part by heparin binding growth factors. We hypothesized that placement of a therapeutic polymer in the periadventitial space capable of tightly binding growth factors might alter the vascular response to injury, We first demonstrated that incubation of rat aortic smooth muscle cells withan insoluble, sulfated polymer of beta-cyclodextrin (P-CDS) was associated with a dose-dependent inhibition of proliferation induced by fetal calf serum, fibroblast growth factor-2 (FGF-2), platelet-derived growth factor BE, of epidermal growth factor, Preincubation studies of P-CDS with FGF-2 revealed a very rapid removal of mitogenic activity, Using radiolabeled FGF-2 (0.25 mu g/ml), we observed a very rapid association rate (0.34+/-0.07 min(-1), n = 4) and a very slow dissociation rate (3.3+/-0.2 x 10(-7) min(-1)) at 37 degrees C, suggesting a high affinity interaction, Using both Transwell and linear under-agarose assays, we demonstrated a significant inhibition of random migration (chemokinesis) by P-CDS, Unsulfated polymeric beta-cyclodextrin (P-CD) hadlittle if any of these effects, suggesting that the high negative charge density of P-CDS was important for the effects, Finally, rats undergoing carotid artery balloon injury were randomized to treatment withperiadventitial P-CDS or no treatment, and were killed at 4 (n = 20),14 (n = 59), and 88 d (n = 14), Morphometric analysis demonstrated significant and sustained inhibition of intimal thickening in P-CDS-treated rats at 14 (P < 0.01) and 88 d (P < 0.05) using absolute intimal area or intima/media area ratios, No inhibition was seen in a group of rats treated with P-CD, In P-CDS - treated rats, bromodeoxyuridine labeling studies revealed fewer labeled smooth muscle cells in the intimaat 14 d (P = 0.01), while staining with Evans blue revealed enhanced late endothelial cell regrowth, Thus, periadventitially applied sulfated beta-cyclodextrin polymer, which can tightly bind heparin binding growth factors, inhibits intimal thickening in vivo in a sustained fashion without using an additional delivery system, These studies suggestthat cellular processes mediated by heparin binding growth factors may be modulated by P-CDS.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/10/20 alle ore 12:49:40