ライフサイエンスコーパス: FVIIa

1 FVIIa binding to EPCR failed to accelerate FVIIa activat

2 FVIIa binding to EPCR is confirmed by demonstrating a ma

3 FVIIa binding to EPCR may promote the endocytosis of thi

4 FVIIa binding to EPCR was shown to facilitate FVIIa endo

5 FVIIa binding to TF induces the internalization of TF.

6 FVIIa binds seven Ca(2+) ions in the Gla, one in the EGF

7 FVIIa caused potentiation of cell repulsion by the EphB2

8 FVIIa-induced p44/42 MAPK activation and the barrier-pro

9 FVIIa/TF activation of each FX mutant and the correspond

10 dentical and similar to those for rTF(1-243)-FVIIa.

11 In FXase, the K(m) of FX for rTF(1-263)-FVIIa remained unchanged after deglycosylation, whereas

12 ameters of FX activation by both rTF(1-263D)-FVIIa and pTF(D)-FVIIa were identical and similar to tho

13 Additional introduction of a FVIIa-M306D mutation to uncouple the sTF-mediated allost

14 fects of the antibodies were retained with a FVIIa variant, which has been shown to be inert to allos

15 FVIIa binding to EPCR failed to accelerate FVIIa activation of factor X or protease-activated recep

16 Accordingly, FVIIa mutants deficient in direct TF-dependent thrombin

17 1 resulted in retention of accumulated AF488-FVIIa in the REC, whereas expression of a dominant negat

18 stitutively active Rab4A, internalized AF488-FVIIa accumulated in early/sorting endosomes and its ent

19 njugated with AF488 fluorescent probe (AF488-FVIIa), and intracellular trafficking of FVIIa, EPCR, an

20 Since APC and FVIIa bind to sEPCR involving similar interactions, we c

21 s beneath the plasma membrane where EPCR and FVIIa accumulated.

22 in the intracellular trafficking of EPCR and FVIIa.

23 ved at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amount

24 e day before measurement decreased FVIIc and FVIIa by 8% and 19.2%, respectively.

25 The combination of FXa and FVIIa maximally enhanced infection for TF(+)/gC(+) HSV1

26 nd postprandial lipid, glucose, insulin, and FVIIa concentrations at baseline and after a 3-wk diet p

27 st, insertions in the 60-loop in plasmin and FVIIa allow Arg-20 of KD1 to directly interact with Glu-

28 titutively express EPCR and TF, thrombin and FVIIa/FX but not FVIIa alone induced PAR1-dependent sign

29 impacts of inhibitor binding to trypsin and FVIIa, as well as cofactor binding to FVIIa.

30 of inhibitors, of a high-activity gene-based FVIIa variant in an animal model of hemophilia.

31 and of great clinical significance, because FVIIa is used clinically for the prevention of bleeding

32 However, soaking benzamidine-FVIIa/sTF crystals with d-Phe-Pro-Arg-chloromethyl keton

33 anion hole is also absent in the benzamidine-FVIIa/sTF structure at 1.87A resolution.

34 (1) the need to overcome competition between FVIIa and FVII zymogen for tissue factor (TF) binding, a

35 properties of TF, a covalent complex between FVIIa and the soluble ectodomain of TF (sTF) was enginee

36 s for the development of orally bioavailable FVIIa inhibitors.

37 roduction of a nonperturbing cystine bridge (FVIIa Q64C-sTF G109C) in the interface.

38 EphB2 was cleaved by FVIIa concentrations in the subnanomolar range in a numb

39 lipid-dependent activations of FIX and FX by FVIIa/TF and inactivation of activated factor V by APC.

40 ism for TF expression at the cell surface by FVIIa.

41 hether gene transfer of an engineered canine FVIIa (cFVIIa) transgene can affect hemostasis in a cani

42 Like aPC, activated coagulation FVIIa can also bind to EPCR.

43 Upon coexpression, FVIIa Q64C and sTF G109C spontaneously assembled into a

44 ndings from these mouse models of continuous FVIIa expression have implications for the development o

45 In contrast, FVIIa/TF activation of FIX(PCGla) was minimally affected

46 cofactor tissue factor (TF), which converts FVIIa from an intrinsically poor enzyme to an active pro

47 ivation by both rTF(1-263D)-FVIIa and pTF(D)-FVIIa were identical and similar to those for rTF(1-243)

48 e/absence of Mg(2+) to FVIIa, Gla-domainless FVIIa, and prothrombin fragment 1 supports the crystal d

49 thromboembolic risk of continuously elevated FVIIa levels.

50 Under physiological conditions, endogenous FVIIa engages its cell-localized cofactor tissue factor

51 FVIIa:sTF interface are proposed to enhance FVIIa activity upon sTF binding.

52 zation and intracellular trafficking of EPCR-FVIIa.

53 tive Rab5A inhibited the endocytosis of EPCR-FVIIa.

54 fficacy and safety of continuously expressed FVIIa as a FVIII/FIX-bypassing agent in a large animal m

55 VIIa binding to EPCR was shown to facilitate FVIIa endocytosis.

56 ole in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cel

57 Recombinant factor FVIIa targets coagulation cascade activation which helps

58 rtant role in the factor VIIa/tissue factor (FVIIa/TF)-induced coagulation.

59 In summary, we report the first FVIIa variant that is catalytically independent of sTF a

60 For FVIIa, in contrast, the protease domain is "locked" into

61 a, revealing gC as a novel PAR2 cofactor for FVIIa.

62 is unusual and has biologic implications for FVIIa macromolecular substrate specificity and catalysis

63 data show that K1 is not only important for FVIIa inhibition but also for FXa inhibition, i.e. for t

64 of 0.3 nmol/kg compared with 300 nmol/kg for FVIIa.

65 implies that the Gla domain is necessary for FVIIa/TF/Ixolaris/FX(a) complex formation.

66 trostatic interactions are weak, whereas for FVIIa, hydrophobic interactions are missing, and electro

67 igh concentration required would result from FVIIa's weak affinity for phospholipids.

68 Furthermore, FVIIa contains a Na(+) and two Zn(2+) sites, but ligands

69 and postprandial changes in activated FVII (FVIIa) concentrations after a 6-mo alteration in dietary

70 ly processed and secreted as activated FVII (FVIIa).

71 Binding analysis revealed that FVII, FVIIa, protein C, and activated protein C (APC) bound to

72 he role of this interaction in clearing FVII/FVIIa from the circulation are unknown.

73 R serves as a cellular binding site for FVII/FVIIa.

74 tissue factor (TF), the interaction of FVII/FVIIa with unperturbed endothelium and the role of this

75 s of these peptides in complex with the FVII/FVIIa protease domain revealed their distinct binding si

76 Although factor VII/factor VIIa (FVII/FVIIa) is known to interact with many non-vascular cells

77 Fasting fibrinogen, FXIIa, FVIIc, FVIIa, and FVII antigen and postprandial FVIIa were not

78 Thrombin combined with FXa/FVIIa enhanced infection, suggesting that PAR1 and PAR2

79 atalytic domains, based on recombinant human FVIIa (rhFVIIa) variants.

80 by demonstrating a marked increase in (125)I-FVIIa binding to CHO cells that had been stably transfec

81 C receptor (EPCR) blocked effectively (125)I-FVIIa binding to HUVEC.

82 (125)I-FVIIa bound to non-stimulated human umbilical vein endot

83 serine proteases, the amide N of Gly(193) in FVIIa points away from the oxyanion hole in this structu

84 nteract with Glu-60 in plasmin and Asp-60 in FVIIa.

85 ys-60A and Arg-60D in plasmin and Lys-60A in FVIIa.

86 ponsible for increased expression of IL-8 in FVIIa-treated cells.

87 ion by a flip of the 192-193 peptide bond in FVIIa.

88 glutamic acid (Gla) domains of FX and FIX in FVIIa/TF induced coagulation, we studied four new and tw

89 ation and functional active site geometry in FVIIa.

90 in a mean 47% (95% CI: 42%, 52%) increase in FVIIa 6 h later, but the response did not differ by n-6:

91 ty, and a 25% lower postprandial increase in FVIIa concentration.

92 h Ca(2+) and Mg(2+), and the Ca(2+) sites in FVIIa that could be specifically occupied by Mg(2+) are

93 ediate crosstalk between functional sites in FVIIa, particularly the cofactor binding site and the ac

94 75 of the basic patch in plasmin, whereas in FVIIa, such interactions are not possible.

95 7, Met-39, and Phe-41 in plasmin, whereas in FVIIa/tissue factor, it is essentially absent.

96 ration and invasion, active site-inactivated FVIIa, and specific antibodies against TF, PAR-2, and IL

97 ension libraries to immobilized and inactive FVIIa.

98 re, we sought to engineer an sTF-independent FVIIa variant by stabilizing both proposed pathways, wit

99 The K1 domain of TFPI binds and inhibits FVIIa and the K2 domain similarly inhibits FXa.

100 of Rab11 led to accumulation of internalized FVIIa in the cytoplasm and prevented entry of internaliz

101 ytoplasm and prevented entry of internalized FVIIa into the REC.

102 To this end, we investigated FVIIa's role in the migration and invasiveness of the br

103 is allosteric communication by investigating FVIIa loop swap variants containing the 170 loop of tryp

104 oration of a methyl group onto a macrocyclic FVIIa inhibitor improves potency 10-fold but is accompan

105 nd synthesized a novel series of macrocyclic FVIIa inhibitors.

106 EPCR-mediated FVIIa endocytosis/recycling also resulted in transport o

107 n vivo, this mutant is as effective as mouse FVIIa in controlling bleeding in hemophilia B mice.

108 viously, we showed that expression of murine FVIIa (mFVIIa) from an adeno-associated viral (AAV) vect

109 recombinant proteins, we showed that murine FVIIa (mFVIIa) and variants had comparable binding to hu

110 B mice following gene transfer of the murine FVIIa homolog, with no evidence of thrombotic complicati

111 s EPCR and TF, thrombin and FVIIa/FX but not FVIIa alone induced PAR1-dependent signaling.

112 C partly enhanced the effect of FXa, but not FVIIa, revealing gC as a novel PAR2 cofactor for FVIIa.

113 PAR1 and PAR2 activation, in the absence of FVIIa, had no effect on TF endocytosis.

114 roach was adopted to enhance the activity of FVIIa by selectively optimizing substrate turnover at th

115 The sTF-independent activity of FVIIa-VY(T) was partly mediated by an increase in the N

116 uctural features determining the activity of FVIIa.

117 with the tryptic serine protease activity of FVIIa.

118 ies using mice showed that administration of FVIIa before lipopolysaccharide (LPS) treatment attenuat

119 nt individual residues in the heavy chain of FVIIa whose conformation and/or local interaction patter

120 nds to the EGF1 domain in the light chain of FVIIa, underscoring a remarkable intra- and interdomain

121 ns of FVII or an equivalent concentration of FVIIa (10 nM).

122 hat are exposed to limited concentrations of FVIIa and FX provided by ectopic synthesis or vascular l

123 the presence of saturating concentrations of FVIIa exhibited similar coagulant activity as that of wi

124 Pharmacological concentrations of FVIIa were found to impair partly the EPCR-dependent pro

125 evealed a novel, nonstandard conformation of FVIIa active site in the region of the oxyanion hole, a

126 of affinities for different conformations of FVIIa.

127 allosteric effects in the protease domain of FVIIa.

128 hemostatic effect of pharmacologic doses of FVIIa is TF independent.

129 ng to EPCR enhances the hemostatic effect of FVIIa in a mouse hemophilia model, when assayed as ferri

130 EPCR contributes to the hemostatic effect of FVIIa in hemophilia.

131 nd metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast

132 h both increased the catalytic efficiency of FVIIa more than 150-fold.

133 sis of TF-mediated allosteric enhancement of FVIIa activity.

134 is available for the free, inactive form of FVIIa that circulates in the blood prior to vascular inj

135 ptide agonists and proteases, independent of FVIIa, mobilized TF from the Golgi store and increased t

136 ed to investigate the potential influence of FVIIa interaction with EPCR in the pathogenesis of hemop

137 scaffolds for Ixolaris in the inhibition of FVIIa/TF and implies that the Gla domain is necessary fo

138 to TFPI effectively prevented inhibition of FVIIa/TF/FXa and improved clot formation in hemophilia b

139 R, and blockade of EPCR reduces the level of FVIIa needed for hemostasis in a saphenous vein bleeding

140 e Rao group showed that hemostatic levels of FVIIa displace PC from EPCR, and blockade of EPCR reduce

141 ought to define safe and effective levels of FVIIa for continuous expression.

142 15-217, we replaced the flexible 170 loop of FVIIa with the more rigid 170 loop from trypsin and comb

143 se-requiring phospholipid-related pathway of FVIIa action.

144 cking antibodies impaired the early phase of FVIIa clearance.

145 methyl group interacts with the S2 pocket of FVIIa.

146 speculate that the allosteric regulation of FVIIa activity by TF binding follows a similar path in c

147 ophysiological consequences and relevance of FVIIa binding to EPCR.

148 e the sTF-mediated allosteric stimulation of FVIIa provided a final complex with FVIIa-like activity

149 sent in x-ray crystallographic structures of FVIIa, which previously only have been hypothesized or i

150 488-FVIIa), and intracellular trafficking of FVIIa, EPCR, and Rab proteins was evaluated by immunoflu

151 docytosis may facilitate the transcytosis of FVIIa and its clearance from the circulation.

152 gative Rab11 also inhibited the transport of FVIIa across the endothelium.

153 osis/recycling also resulted in transport of FVIIa from the apical to the basal side.

154 lications for the molecular understanding of FVIIa regulatory mechanisms.

155 This process is dependent on FVIIa protease activity.

156 Upon altering pH and adding TF to switch on FVIIa enzymatic activity, only those phage released by p

157 (2+) condition, sEPCR binding to APC-Gla (or FVIIa-Gla) replaces Mg4 by Ca4 with an attendant conform

158 or postprandial lipid, glucose, insulin, or FVIIa concentrations.

159 Ic, FVIIa, and FVII antigen and postprandial FVIIa were not influenced by the diets.

160 that, compared with other serine proteases, FVIIa is uniquely equipped to accommodate conformational

161 ease, 4-fold, in k(cat) was observed for pTF.FVIIa upon deglycosylation, whereas the K(m) was minimal

162 ch potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate fac

163 tudy we examined the binding of radiolabeled FVIIa to endothelial cells and its subsequent internaliz

164 nd the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients.

165 thropathy and its treatment with recombinant FVIIa (rFVIIa).

166 and combined it with an L163V substitution (FVIIa-VY(T)).

167 of FX with human or mouse tissue factor (TF)-FVIIa complexes.

168 formation of a quaternary tissue factor (TF)/FVIIa/ FX(a)/Ixolaris inhibitory complex.

169 In ex vivo flowing blood, a TF-FVIIa mutant complex with impaired free FXa generation b

170 AR-2-specific antibodies fully attenuated TF-FVIIa-induced IL-8 expression.

171 omplex but did not alter PAR2 cleavage by TF-FVIIa.

172 -FXa complex but not by the non-coagulant TF-FVIIa binary complex.

173 e tissue factor (TF)/factor VIIa complex (TF-FVIIa) are promising novel anticoagulants which show exc

174 chanism and tissue factor-activated FVII (TF-FVIIa) via formation of a quaternary FXa-TFPI-TF-FVIIa c

175 ies against TF, PAR-2, and IL-8 inhibited TF-FVIIa-induced cell migration.

176 ity on the cell surface, while inhibiting TF-FVIIa signaling that leads to proangiogenic cytokine exp

177 Moreover, nascent FXa product of TF-FVIIa can transiently escape the slow kinetics of Kunitz

178 factor VIIa (FVIIa), and the formation of TF-FVIIa complexes on cell surfaces triggers the activation

179 The formation of TF-FVIIa complexes on cell surfaces triggers the activation

180 rin trafficking increases availability of TF-FVIIa with procoagulant activity on the cell surface, wh

181 by TFPI (EC50 = 11 nM) and inhibition of TF-FVIIa-catalyzed FX activation by TFPI (EC50 = 2 nM).

182 NA and activity and the colocalization of TF-FVIIa-FXa-TFPI with caveolin-1.

183 ncreases the TFPI-dependent inhibition of TF-FVIIa.

184 t mutation in this motif markedly reduces TF-FVIIa association with integrins, attenuates integrin tr

185 o a series of highly potent and selective TF-FVIIa inhibitors which displayed poor permeability.

186 ely blocked PAR activation by the ternary TF-FVIIa-FXa complex but not by the non-coagulant TF-FVIIa

187 a) via formation of a quaternary FXa-TFPI-TF-FVIIa complex.

188 Of interest, we found that TF-FVIIa complex formation at the cell surface leads to TF

189 ditional in vitro experiments showed that TF-FVIIa promoted tumor cell migration and invasion, active

190 sma protease factor VIIa (FVIIa), and the TF-FVIIa complex initiates coagulation in both hemostasis a

191 structural basis for the crosstalk of the TF-FVIIa complex with integrin trafficking and suggest a cr

192 n that is required for association of the TF-FVIIa complex with the active conformer of integrin beta

193 ors X and IX through the formation of the TF-FVIIa-FXa-TFPI complex.

194 (TFPI) blocks tissue factor-factor VIIa (TF-FVIIa) activation of factors X and IX through the format

195 r inhibitor of tissue factor-factor VIIa (TF-FVIIa)-dependent FXa generation.

196 In vitro, FXa stably associated with TF-FVIIa activates FVIII, but not FV.

197 TF.FVIIa is also implicated in thrombosis-related disorders

198 of this signaling pathway is required for TF.FVIIa.Xa-induced cell migration, invasion, and metastasi

199 el role of MDA-9/syntenin as an important TF.FVIIa.Xa/PAR-1-regulated gene that initiates a signaling

200 ike serine proteases, consistent with its TF.FVIIa-specific activity in clotting assays.

201 es are potent and selective inhibitors of TF.FVIIa, neither showed 100% inhibition at saturating conc

202 In these contexts, targeting TF.FVIIa.Xa and its relevant downstream targets such as MDA

203 905, which displayed great potency toward TF.FVIIa (Ki = 0.35 +/- 0.11 nM).

204 g process, the tissue factor-factor VIIa (TF.FVIIa) complex.

205 mily were cleaved in their ectodomains by TF/FVIIa.

206 n further support of a direct cleavage by TF/FVIIa.

207 F/FVIIa and provide new insights into how TF/FVIIa regulates cellular functions independently of PAR2

208 nt of tyrosine kinase receptors (RTKs) in TF/FVIIa signaling by antibody array analysis and subsequen

209 ph RTKs as novel proteolytical targets of TF/FVIIa and provide new insights into how TF/FVIIa regulat

210 Our results suggest that TF/FVIIa/PAR2 signaling mediates neutrophil activation and

211 of TFPI-/- embryos was due to unregulated TF/FVIIa activity and that the hemostatic defects in low-TF

212 tors FXa (via TF/VIIa or FIXa), FIXa (via TF/FVIIa or FXIa), thrombin, fibrin, and FXIa.

213 methyl groups provided a macrocycle with TF/FVIIa Ki = 1.6 nM, excellent selectivity against a panel

214 In addition, TF:FVIIa-dependent activation of PAR2 on tumor cells increa

215 R2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cell

216 rodrugs that are selectively activated by TF:FVIIa, FXa, and thrombin.

217 e PAR2 by physiological concentrations of TF:FVIIa and FXa.

218 Mab, that induced efficient inhibition of TF:FVIIa-dependent intracellular signaling, antibody-depend

219 The TF:FVIIa complex also activates cells by cleavage of a G-pr

220 Initial studies using inhibitors of the TF:FVIIa complex in mouse tumor models have produced encour

221 Treatment with the TF:FVIIa inhibitor led to growth retardation in breast tumo

222 ited 60-fold higher amidolytic activity than FVIIa, and displayed similar FX activation and antithrom

223 show that FXa(I16L) is more efficacious than FVIIa, which is used to treat bleeding in hemophilia inh

224 tments, predominantly in the Golgi, and that FVIIa binding to cell surface TF induces TF endocytosis

225 rall, our present data provide evidence that FVIIa bound to EPCR on endothelial cells activates PAR1-

226 with previous observations, we observed that FVIIa increased the migratory and invasive potential of

227 Overall, our results show that FVIIa or activated protein C binding to EPCR promotes EP

228 In the present study, we show that FVIIa, upon binding to EPCR on endothelial cells, activa

229 Others suggest that FVIIa binds platelets where it activates FX directly; th

230 Some studies suggest that FVIIa requires tissue factor (TF) for function and that

231 The FVIIa-VYT variant exhibited 60-fold higher amidolytic ac

232 e PAR2 receptor, and not PAR1, abrogated the FVIIa-mediated TF mobilization.

233 osteric activation pathways originate at the FVIIa:sTF interface are proposed to enhance FVIIa activi

234 n knockdown almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and

235 neutralizing antibodies fully attenuated the FVIIa-induced TF mobilization.

236 2 activation is found to be critical for the FVIIa-induced TF endocytosis.

237 To this end, we generated the FVIIa active site inhibitor G17905, which displayed grea

238 ructure of a closely related analogue in the FVIIa active site was obtained and matches the NMR and m

239 tes allosteric conformational changes in the FVIIa protease domain and improves its catalytic propert

240 -Gly-Glu (KGE) integrin-binding motif in the FVIIa protease domain that is required for association o

241 ondition was necessary to replace Mg4 in the FVIIa/soluble TF structure.

242 tivated factor X (FXa) and also inhibits the FVIIa-TF complex.

243 ggested that a C-terminal extension into the FVIIa active site could yield a chimeric inhibitor that

244 Mutagenesis of the FVIIa 4-carboxyglutamic acid domain and dose titrations

245 n is pivotal to the enhanced activity of the FVIIa variants.

246 The crystal structure of the FVIIa.G17905 complex provides insight into the molecular

247 and antithrombin inhibition kinetics to the FVIIa.sTF complex.

248 oop from trypsin directly interacts with the FVIIa active site, stabilizing segment 215-217 and activ

249 This FVIIa-induced, barrier-protective effect was EPCR depend

250 binding in the presence/absence of Mg(2+) to FVIIa, Gla-domainless FVIIa, and prothrombin fragment 1

251 reover, since phospholipid and sEPCR bind to FVIIa or APC via the omega-loop, we predict that phospho

252 ies, Mg(2+) enhanced phospholipid binding to FVIIa and APC at physiological Ca(2+).

253 TF binding to FVIIa furthermore results in stabilization of the 170 lo

254 in and FVIIa, as well as cofactor binding to FVIIa.

255 arable with FIX but not FX in its binding to FVIIa/TF.

256 Cells were exposed to FVIIa conjugated with AF488 fluorescent probe (AF488-FVI

257 f-magnitude increase in activity relative to FVIIa upon exposure to a procoagulant membrane.

258 Binding of TF to FVIIa promotes allosteric conformational changes in the

259 its constitutively active ancestor trypsin, FVIIa is allosterically activated (by TF).

260 A, FXa, plasmin, plasma kallikrein, trypsin, FVIIa).

261 onoclonal antibody and activated factor VII (FVIIa) binding studies showed that little TF protein was

262 insulin, and activated clotting factor VII (FVIIa) concentrations.

263 n of recombinant human activated Factor VII (FVIIa) has been used for over a decade in the successful

264 ntinuous expression of activated factor VII (FVIIa) via gene transfer is a potential therapeutic appr

265 tic domain variants of activated factor VII (FVIIa) with enhanced hemostatic properties are highly at

266 cessful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor

267 ctivated coagulation factors X (FXa) or VII (FVIIa) directly affect HSV1 infection of human umbilical

268 ypsin-like protease coagulation factor VIIa (FVIIa) and its cofactor tissue factor (TF), which conver

269 e recently showed that clotting factor VIIa (FVIIa) binding to endothelial cell protein C receptor (E

270 t studies have established that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor

271 Recent studies have shown that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor

272 e amidolytic activity of the TF.factor VIIa (FVIIa) complex toward a fluorogenic substrate showed tha

273 Factor VIIa (FVIIa) consists of a gamma-carboxyglutamic acid (Gla) do

274 we demonstrate that coagulation factor VIIa (FVIIa) elicits TF cytoplasmic domain-dependent proangiog

275 The serine protease factor VIIa (FVIIa) in complex with its cellular cofactor tissue fact

276 Factor VIIa (FVIIa) is a trypsin-like protease that plays an importan

277 and the plasma serine protease factor VIIa (FVIIa) mediates the initiation of blood coagulation.

278 Factor VIIa (FVIIa) or activated protein C binding to EPCR promoted t

279 tissue factor (TF), coagulation factor VIIa (FVIIa) predominantly exists in a zymogen-like, catalytic

280 ation, but potently inhibits TF/Factor VIIa (FVIIa) signaling through PAR2, inhibited aPL-induced neu

281 (TF) binds the serine protease factor VIIa (FVIIa) to form a proteolytically active complex that can

282 Recombinant factor VIIa (FVIIa) variants with increased activity offer the promis

283 The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bou

284 cellular receptor for clotting factor VIIa (FVIIa), and the formation of TF-FVIIa complexes on cell

285 ar receptor for plasma protease factor VIIa (FVIIa), and the TF-FVIIa complex initiates coagulation i

286 (TF), the cellular receptor for factor VIIa (FVIIa), besides initiating blood coagulation, is believe

287 , activated protein C, plasmin, factor VIIa (FVIIa), FIX, FIXa, and FXII.

288 cellular receptor for clotting factor VIIa (FVIIa).

289 lular signaling in complex with factor VIIa (FVIIa).

290 inhibits trypsin, plasmin, and factor VIIa (FVIIa)/tissue factor with Ki values of 13, 3, and 1640 n

291 of coagulation by inhibition of Factor VIIa (FVIIa)/tissue factor/Factor Xa (FVIIa/TF/FXa).

292 C generation is the major mechanism by which FVIIa interaction with EPCR contributes to the hemostati

293 Pretreatment of endothelial cells with FVIIa protected against thrombin-induced barrier disrupt

294 ation of FVIIa provided a final complex with FVIIa-like activity in solution, while exhibiting a two

295 coagulantly active once it is complexed with FVIIa, and TF de-encryption does not require Cys186-Cys2

296 g a chimera of mouse FIX (Gla and EGF1) with FVIIa (EGF2 and catalytic domain) into hemophilia B mice

297 n of protein C prevents its interaction with FVIIa/TF.

298 ent of confluent endothelial monolayers with FVIIa before thrombin reduced the development of thrombi

299 F1 domains of FX interact more strongly with FVIIa/TF than the corresponding domains in FIX.

300 TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacolo

301 Factor VIIa (FVIIa)/tissue factor/Factor Xa (FVIIa/TF/FXa).