Antiangiogenic plasma activity in patients with systemic sclerosis.

Antiangiogenic plasma activity in patients with systemic sclerosis. Research Abstract Details 

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Antiangiogenic plasma activity in patients with systemic sclerosis. Abstract Text:

Mary Jo Mulligan-Kehoe,Mary C Drinane,Jessica Mollmark,Livia Casciola-Rosen,Laura K Hummers,Amy Hall,Antony Rosen,Fredrick M Wigley,Michael Simons,Mary Jo Mulligan-Kehoe,Mary C Drinane,Jessica Mollmark,Livia Casciola-Rosen,Laura K Hummers,Amy Hall,Antony Rosen,Fredrick M Wigley,Michael Simons,

OBJECTIVE: Systemic sclerosis (SSc; scleroderma) is a systemic connective tissue disease with an extensive vascular component that includes aberrant microvasculature and impaired wound healing. The aim of this study was to investigate the presence of antiangiogenic factors in patients with SSc. METHODS: Plasma samples were obtained from 30 patients with SSc and from 10 control patients without SSc. The samples were analyzed for the ability of plasma to affect endothelial cell migration and vascular structure formation and for the presence of antiangiogenic activity. RESULTS: Exposure of normal human microvascular dermal endothelial cells to plasma from patients with SSc resulted in decreased cell migration (mean +/- SEM 52 +/- 5%) and tube formation (34 +/- 6%) compared with that in plasma from control patients (P < 0.001 for both). SSc plasma contained 2.9-fold more plasminogen kringle 1-3 fragments (angiostatin) than that in control plasma. The addition of angiostatin to control plasma resulted in inhibition of endothelial cell migration and proliferation similar to that observed in SSc plasma. In vitro studies demonstrated that granzyme B and other proteases contained in T cell granule content cleave plasminogen and plasmin into angiostatin fragments. CONCLUSION: Plasminogen conformation in patients with SSc enables granzyme B and granule content protease to limit the proangiogenic effects of plasmin and increase the levels of antiangiogenic angiostatin. This increase in angiostatin production may account for some of the vascular defects observed in patients with SSc.

Antiangiogenic plasma activity in patients with systemic sclerosis. Publishing Authors By Initials

MJ Mulligan-Kehoe,MC Drinane,J Mollmark,L Casciola-Rosen,LK Hummers,A Hall,A Rosen,FM Wigley,M Simons,MJ Mulligan-Kehoe,MC Drinane,J Mollmark,L Casciola-Rosen,LK Hummers,A Hall,A Rosen,FM Wigley,M Simons,

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Antiangiogenic plasma activity in patients with systemic sclerosis. Journal Published:

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

Journal: Arthritis and rheumatism

VOLUME: 56

Page Numbers: 3448-58

Journal Abbreviation: Arthritis Rheum.

ISSN: 0004-3591

DAY: 22

MONTH: Oct

YEAR: 2007

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LANGUAGE: eng

NlmUniqueID: 370605

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Grant and Affiliation Information for Antiangiogenic plasma activity in patients with systemic sclerosis.

AFFILIATION: Angiogenesis Research Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL-62289

ACRONYM: HL

MEDLINETA: Arthritis Rheum

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