Decreased monocyte-mediated angiogenesis in scleroderma

Koch, Alisa E.; Litvak, Michael; Burrows, James C.; Polverini, Peter J.

doi:10.1016/0090-1229(92)90193-r

Cited by 23 publications

(17 citation statements)

References 29 publications

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“…Several studies have demonstrated angiogenesis-related abnormalities, including decreased monocyte-mediated angiogenesis (35) and the presence of proangiogenic and antiangiogenic factors in SSc serum (36), including increased levels of circulating endostatin (37,38). At the same time, SSc serum was reported to enhance the angiogenic capability of circulating mononuclear cells (39).…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic plasma activity in patients with systemic sclerosis

Mulligan-Kehoe¹,

Drinane²,

Mollmark³

et al. 2007

Arthritis & Rheumatism

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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.

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Section: Discussionmentioning

confidence: 99%

Antiangiogenic plasma activity in patients with systemic sclerosis

Mulligan-Kehoe¹,

Drinane²,

Mollmark³

et al. 2007

Arthritis & Rheumatism

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“…LIF induced a weaker effect (1.18-fold for 475 pmol/L, PϽ0.05, nϭ3), but IL-6 did not induce any change in uPAR expression (Table 3). 5 ) were seeded in the upper chamber of a 3-m-porediameter Transwell-Col, and cytokines at indicated concentration were added in the lower compartment to test their chemotractant activity. After a 24 hour-incubation, cells on the lower face of the membrane were scraped, added to the cells in the lower compartment, and then counted in a hemocytometer.…”

Section: Variation Of Upar Expression On the Hmec-1 Surface By Osmmentioning

confidence: 99%

“…Cells (2ϫ10 5 ) were seeded in the upper chamber of a Transwell-Col insert (collagen-coated membrane with 3-m-diameter pores; Dutcher). The lower chamber was filled with 1 mL of MCDB-131, together with 2 mg/mL BSA and the cytokine to be tested.…”

Section: Chemotaxis Assay On a Collagen-coated Membranementioning

confidence: 99%

“…1,2 However, recent evidence also suggests that capillary regression may be mediated by monocytes by producing antiangiogenic factors in vitro and in vivo. [3][4][5] Thus, macrophages could be involved in both stimulation and suppression of angiogenesis.Because macrophages reside at the sites of atherosclerotic plaques in the vessel wall and because the formation of highly vascularized granulations could be responsible for the fragility of the plaque, 6 we were prompted to analyze the effects of oncostatin M (OSM) on neovascularization. OSM, secreted by activated monocytes, is a cytokine of the interleukin-6 (IL-6) family that includes IL-6, leukemia inhibitory factor (LIF), and ciliary neurotrophic factor.…”

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confidence: 99%

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Oncostatin M Induces Angiogenesis In Vitro and In Vivo

Vasse

Pourtau

Trochon

et al. 1999

ATVB

121

101

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Abstract-Neovascularization of the atherosclerotic plaque is responsible for its weakening and consequently for the complications of vascular disease. Macrophages are a source of growth factors that can modulate angiogenesis. In this study, we analyzed the effect of oncostatin M (OSM) on angiogenesis, as it could be involved in the development of atherosclerosis. The effect of OSM was compared with those of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). On human dermal microvasculature endothelial cells (HMEC-1s), OSM (22.5 to 112.5 pmol/L) induced a dose-dependent increase in cell proliferation greater than that induced by the classic angiogenic factors vascular endothelial growth factor (VEGF; 543 pmol/L) and basic fibroblast growth factor (bFGF; 1.1 nmol/L). LIF (19 to 475 pmol/L) induced only a 30% increase in cell proliferation, and IL-6 had no effect. Furthermore, in a modified Boyden-chamber model, OSM, LIF, and IL-6 were chemoattractant for HMEC-1s. In a tridimensional gel of fibrin, OSM increased tube formation and tube length, which were already noticeable by day 3. LIF and IL-6 induced a weaker effect that was only obvious by day 10. The angiogenic effect of OSM was also demonstrated in vivo in a rabbit corneal model: OSM was more potent than LIF, the length of the neovessels being longer with OSM than with LIF, whereas IL-6 was without effect. We tested factors that could be involved in the proliferative effect of OSM on HMEC-1s. OSM induced only a slight increase in the urokinase receptor and a 60% increase in VEGF secretion, whereas it does not modify IL-8 secretion or bFGF levels. The effect of OSM seems to depend on endothelial cell origin and cell species: OSM (up to 112.5 pmol/L) did not induce human umbilical vein endothelial cell proliferation and even had a small inhibitory effect (17%) on calf pulmonary artery endothelial cells. In conclusion, OSM induces an angiogenic effect on capillary endothelial cells, which could be, at least in part, implicated in pathological processes such as atherosclerosis or tumor growth. Key Words: angiogenesis Ⅲ atherosclerosis Ⅲ oncostatin M Ⅲ leukemia inhibitory factor Ⅲ vascular endothelial growth factor I t is now established that the functional role of the macrophage extends far beyond its originally recognized role as a scavenger cell. Monocytes in particular are recognized as angiogenesis effector cells that produce a number of growth stimulators and inhibitors, proteolytic enzymes, and cytokines that can influence 1 or more steps in the angiogenesis cascade. It has been shown that activated monocytes or their culture supernatants induce new capillary growth in vitro and angiogenesis in vivo. 1,2 However, recent evidence also suggests that capillary regression may be mediated by monocytes by producing antiangiogenic factors in vitro and in vivo. [3][4][5] Thus, macrophages could be involved in both stimulation and suppression of angiogenesis.Because macrophages reside at the sites of atherosclerotic plaques in the vessel wall and because the...

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Increased concentrations of the circulating angiogenesis inhibitor endostatin in patients with systemic sclerosis

Hebbar

Peyrat

Hornez

et al. 2000

Arthritis & Rheumatism

123

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Objective. Endostatin is an angiogenesis inhibitor derived from type XVIII collagen. The aim of this study was to determine the concentrations of circulating en-dostatin in patients with systemic sclerosis (SSc), and to assess the relationship between these concentrations, extension of tissular sclerosis, and presence of cutane-ous scars or ulcers. Methods. The study involved 50 patients with SSc and 30 healthy subjects. Cutaneous extension of sclerosis was graded according to Barnett's classification system: 33 patients had grade I SSc and 17 patients had grades II or III SSc. The results of pulmonary function tests were abnormal in 31 of 50 patients, 8 of whom also had abnormalities on chest radiograms. Cutaneous scars or ulcers were found in 22 of 50 patients. Endosta-tin concentrations were determined using a competitive enzyme immunoassay method. Results. The mean circulating endostatin concentration was significantly higher in the SSc group than in the healthy subjects group (mean SD 53.2 22.4 ng/ml versus 9.9 9.7 ng/ml; P < 10-4), in patients with grade II or grade III SSc than in patients with grade I SSc (63.2 20.2 ng/ml versus 45.1 15.6 ng/ml; P < 10-2), in patients with abnormal findings on chest radiograms than in patients with normal findings on chest radiograms (67.6 22.4 ng/ml versus 50.4 21.6 ng/ml; P < 0.05), and in patients with cutaneous scars or ulcers than in patients without these manifestations (60.9 25.9 ng/ml versus 47.2 13.3 ng/ml; P < 10-2). Conclusion. Circulating endostatin concentrations are significantly increased in patients with SSc.

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Decreased monocyte-mediated angiogenesis in scleroderma

Cited by 23 publications

References 29 publications

Antiangiogenic plasma activity in patients with systemic sclerosis

Antiangiogenic plasma activity in patients with systemic sclerosis

Oncostatin M Induces Angiogenesis In Vitro and In Vivo

Increased concentrations of the circulating angiogenesis inhibitor endostatin in patients with systemic sclerosis

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