当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY期刊下所有文献 > 2.5 kDa and 5.0 kDa heparin fragments specifically inhibit microvessel sprouting and network formation in VEGF165-mediated mammalian angiogenesis.

2.5 kDa and 5.0 kDa heparin fragments specifically inhibit microvessel sprouting and network formation in VEGF165-mediated mammalian angiogenesis.

Abstract：

:Tumour growth is angiogenesis dependent. Thrombosis and thromboembolism are very common in cancer patients. These patients are often treated with heparin as an anti-coagulant. Many tumour angiogens, including VEGF165, and endogenous anti-angiogenesis factors bind heparin tightly. Using the non-surgical mesenteric-window angiogenesis assay, we studied in detail the systemic effect of heparin fractions with a mean MW of 2.5, 5.0 and 16.4 kDa on the microvessel sprouting and network formation in angiogenesis mediated by VEGF165 in rats. The microvessel network was assessed objectively in terms of the number and lengths of segments (the distance between two successive branching points), the number of branching points, the degree of tortuosity, the index of interconnecting loop formation, the index of intersection, as well as the number and lengths of sprouts. Compared with the saline control, the 2.5 kDa fraction significantly shortened the microvessel sprouts and the microvessel segments but increased the microvessel tortuosity in statistical terms; the 5.0 kDa fraction statistically significantly shortened the sprouts, decreased the number of segments and the number of microvessel branching points; whereas the 16.4 kDa fraction statistically significantly elongated the longest segments. Moreover, statistically significant differences were found between the three heparin fractions in terms of microvessel tortuosity (2.5 vs. 16.4 kDa), index of loop formation (5.0 vs. 2.5 + 16.4 kDa) and index of intersection (5.0 vs. 16.4 kDa). These findings demonstrate that heparin fragments size-specifically inhibit microvessel sprouting and network formation in VEGF165-mediated angiogenesis. As VEGF165 is a potent angiogen in human tumours, we suggest that heparin enriched in 2.5 kDa species and 5.0 kDa species especially should be exploited as a combined anti-coagulant and specific adjuvant anti-angiogenic agent in cancer patients who require anti-coagulant therapy.

journal_name

Int J Exp Pathol

journal_title

International journal of experimental pathology

authors

Norrby K

doi

10.1046/j.1365-2613.2000.00150.x

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

191-8

issue

eissn

0959-9673

issn

1365-2613

pii

iep150

journal_volume

pub_type

杂志文章

在线工具

2.5 kDa and 5.0 kDa heparin fragments specifically inhibit microvessel sprouting and network formation in VEGF165-mediated mammalian angiogenesis.