Factors relevant to stimulatory activity of fibrin degradation products in vivo

Wd, Thompson; Eb, Smith; Cm, Stirk; Aj, Stout; Kochhar, Abha

doi:10.1097/00001721-199010000-00029

Cited by 8 publications

(3 citation statements)

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“…Several indirect findings support the concept that fibrin(ogen) might be critical for the formation of granulation tissue in wound fields, including: (1) fibrin(ogen) is a prominent component of early wound fields; (2) endothelial cells, fibroblasts, smooth muscle cells, and inflammatory cells can bind fibrin(ogen) through a variety of integrin and nonintegrin receptors 2,3 ; (3) fibrin matrices prepared in vitro and then implanted into experimental animals support the rapid ingrowth of neovasculature in vivo 6,17 ; (4) specific proteolytic derivatives of fibrin have been shown to be angiogenic 18,19 ; and (5) several angiogenic growth factors (FGF-2 and VEGF) interact with fibrin(ogen) with high affinity. 4,5 Nevertheless, the findings presented here show that fibrinogen-deficient mice form copious, highly-vascularized granulation tissue in response to injury which at the level of light microscopy is qualitatively similar to that observed in control mice.…”

Section: Discussionmentioning

confidence: 99%

Wound-healing defects in mice lacking fibrinogen

Drew

2001

Blood

177

135

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In addition to its key role in the control of blood loss following injury, fibrin(ogen) has been proposed to play an important role in tissue repair by providing an initial matrix that can stabilize wound fields and support local cell proliferation and migration. To test directly these concepts, the effect of fibrinogen deficiency on cutaneous tissue repair in mice was investigated using incisional and excisional wounds. The time required to overtly heal wounds was similar in fibrinogen-deficient and control mice, but histologic evaluation revealed distinct differences in the repair process, including an altered pattern of epithelial cell migration and increased epithelial hyperplasia. Furthermore, granulation tissue in fibrinogen-deficient mice failed to adequately close the wound gap, resulting in persistent open wounds or partially covered sinus tracts. The tensile strength of these wounds was also reduced compared with control mice. The most profound defect in wound tissue organization was observed in fibrinogen-deficient mice following the subcutaneous implantation of a porous tubing chamber. Cells migrated into the wall of the implants at a similar rate as control mice, but cells from fibrinogen-deficient animals were unable to efficiently organize and migrate into wound fluid-filled dead space within the center of the implants. These studies show that re-epithelialization, granulation tissue formation, including the establishment of neovasculature, and the formation of fibrotic scar tissue can proceed in the absence of fibrin(ogen) and all of its proteolytic derivatives. However, fibrin (ogen) is important for appropriate cellular migration and organization within wound fields and in initially establishing wound strength and stability. (Blood. 2001;97:3691-3698)

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Section: Discussionmentioning

confidence: 99%

Wound-healing defects in mice lacking fibrinogen

Drew

2001

Blood

177

135

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“…Recently we have identified fibrin fragment E as the active constituent. 32 Fibrinogen fragment E is inactive. The activity of extracts of progressive human atherosclerotic plaques is removed by antifibrinogen affinity chromatography, and more specifically, it is removed by an anti-fra ment E but not an antifragment D coIumn:6.'…”

Section: Discussionmentioning

confidence: 99%

Fibrinolysis and angiogenesis in wound healing

Thompson

Harvey

Kazmi

et al. 1991

The Journal of Pathology

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The healing wound offers a clear example of the sequence of events in chronic inflammation leading to repair. Although angiogenesis has an obvious and essential role in this process, it has been little studied. For an angiogenic factor to seem relevant, it would have to be shown to precede the peak of increased vascularity. To define this peak, the vessel content of simple, incised mouse wounds was estimated using morphometry of histological sections, and found to rise to a maximum at days 5 and 6. Total angiogenic activity of aqueous extracts was found to reach a peak at day 3. The detection of such activity on the chick chorioallantoic membrane is very dependent on the preparation technique and the choice of proteinase inhibitors. Previous in vitro work by us using purified material has shown fibrin degradation products to be effective in stimulating angiogenesis. Fibrin degradation products are prominent on immunoblotting from day 3, when macrophages are plentiful, with a similar band pattern to human granulation tissue.

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“…We have shown previously that fibrin degradation products (FDP), obtained from wound extracts [2], atherosclerotic lesion extracts [3] and clot lysis 141, can stimulate cell proliferation in and in vivo test system the chick chorioallantoic membrane (CAM). Using affmity columns the cell proliferative activity was shown to reside mainly in the fragment E of fibrin [4].…”

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confidence: 99%