A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice.

A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. Research Abstract Details 

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A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. Abstract Text:

Marina Jerebtsova,Edward Wong,Ronald Przygodzki,Pingtao Tang,Patricio E Ray,

Pentosan polysulfate (PPS) is a heparin-like polysaccharide that can affect the binding interactions of fibroblast growth factor (FGF-2) with its high-affinity receptors. Patients with angiogenic tumors frequently show high levels of FGF-2 in the circulation. Since FGF-2 is a heparin-binding angiogenic growth factor, PPS has been used successfully to block its activity in patients with angiogenic tumors. However, because of its heparin-like activity, the major toxic effect of PPS is the development of bleeding disorders. The role that circulating FGF-2 plays in the pathogenesis of bleeding disorders in patients treated with PPS is currently unknown. Here we hypothesized that FGF-2 might play a physiological role in the pathogenesis of intestinal bleeding induced by PPS. This hypothesis is supported by previous studies showing that PPS is accumulated in the intestine and that circulating FGF-2 specifically binds to and modulates the angiogenic activity of intestinal submucosal endothelial cells. We used recombinant adenoviral vectors carrying a secreted form of FGF-2 and LacZ control vectors to determine whether high levels of circulating FGF-2 facilitate the development of intestinal bleeding disorders in FVB/N and C57BL/6J mice treated with PPS. We found that PPS, acting together with FGF-2, induced structural changes in intestinal vessels leading to the development of lethal intestinal hemorrhages. These findings might have wider clinical implications for the systemic use of PPS and other heparinoids in the treatment of patients with angiogenic diseases associated with high levels of circulating FGF-2.

A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. Publishing Authors By Initials

M Jerebtsova,E Wong,R Przygodzki,P Tang,PE Ray,

For similar natural sciences: time: time factors research abstracts see: natural sciences: time: time factors research

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A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of physiology. Heart and circulat

VOLUME: 292

Page Numbers: H743-50

Journal Abbreviation: Am. J. Physiol. Heart Circ. Ph

ISSN: 0363-6135

DAY: 27

MONTH: 10

YEAR: 2006

A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. Information

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LANGUAGE: eng

NlmUniqueID: 100901228

A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. Keywords Mesh Terms:

KEYWORDS: Time Factors

MESH TERMS: metabolism

Chemical & Substance for Abstract: A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. Information

Substance Name: Pentosan Sulfuric Polyester

Registry Number: 37300-21-3

Grant and Affiliation Information for A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice.

AFFILIATION: Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.

Country: United States

AGENCY: United States NCI

GRANT: R21-CA-109011

ACRONYM: CA

MEDLINETA: Am J Physiol Heart Circ Physio

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