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An activated factor VII variant with enhanced tissue factor-independent activity speeds wound healing in a mouse hemophilia B model.

dc.contributor.author Hoffman, Maureane Richardson
dc.contributor.author Chang, J-Y
dc.contributor.author Ezban, M
dc.contributor.author Monroe, DM
dc.coverage.spatial England
dc.date.accessioned 2018-01-01T14:59:48Z
dc.date.available 2018-01-01T14:59:48Z
dc.date.issued 2016-06
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/26952654
dc.identifier.uri http://hdl.handle.net/10161/15926
dc.description.abstract UNLABELLED: Essentials Disorders of hemostasis can lead to delayed and defective wound healing. In hemophilia B (HB) mice, 7 days of Factor (F)IX or VIIa are needed to normalize wound healing. One dose of a highly active FVIIa variant (DVQ) restored normal wound closure time in HB mice. Coagulation factors with enhanced activity may acquire biological effects not due to hemostasis. SUMMARY: Introduction We have previously reported that hemophilia B (HB) mice have delayed healing of cutaneous wounds and alterations in wound histology. Administration of a single dose of either factor IX or recombinant activated FVII (rFVIIa) (NovoSeven) prior to wounding did not improve wound closure time or histology. The FVIIa analog DVQ (V158D, E296V and M298Q mutations) was designed to have higher tissue factor-independent activity than rVIIa. We hypothesized that a single dose of DVQ would be more effective in restoring wound healing in HB mice. Methods Cutaneous punch wounds were made on the backs of HB and wild-type mice, and the time to wound closure was monitored. HB mice were treated with a dose of rFVIIa (10 mg kg(-1) ) or DVQ (1 mg kg(-1) ) that corrected the tail bleeding time. Skin samples were taken at various time points after wounding, fixed, and stained, and the histology was examined. Results As previously reported, wound closure times in HB mice given one dose of rFVIIa were not improved over those in untreated HB mice. Surprisingly, healing times in HB mice treated with an equally hemostatic dose of DVQ were normalized to that in wild-type mice. However, DVQ did not correct all histologic abnormalities in HB mice. Conclusions As the doses of DVQ and rFVIIa were chosen to support comparable levels of hemostasis, our data suggest that the improved healing seen with DVQ is not solely attributable to its hemostatic activity. It is possible that the improved wound healing arises through the effect of DVQ on cell signaling mechanisms.
dc.language eng
dc.relation.ispartof J Thromb Haemost
dc.relation.isversionof 10.1111/jth.13311
dc.subject angiogenesis inhibitors
dc.subject epithelium
dc.subject hemophilia
dc.subject hemostasis
dc.subject thrombin
dc.title An activated factor VII variant with enhanced tissue factor-independent activity speeds wound healing in a mouse hemophilia B model.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/26952654
pubs.begin-page 1249
pubs.end-page 1254
pubs.issue 6
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Immunology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Temp group - logins allowed
pubs.publication-status Published
pubs.volume 14
dc.identifier.eissn 1538-7836


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