Protein C activation in endothelial cells is inhibited under the presence of anticardiolipin antibody in ischemic stroke patients
| Project/Area Number |
07670731
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Tokai University |
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Principal Investigator |
KITAGAWA Yasuhisa Tokai Univ.Associate Prof., 医学部, 助教授 (30124944)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Masahiro Tokai Univ.Associate Prof., 医学部, 助教授 (80095661)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | anticardiolipin antibody / cerebral infaretion / protein C / endothelial cell / antiphospholipid antibody / thrombosis / プロテインC |
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| Research Abstract |
INTRODUCTION : Anticardiolipin antibody (aCL) is considered to be one of the contributory factors in the development of cerebral infarction. A number of sites exist in the coagulation system where interaction with aCL may lead to thrombosis. However, the precise mechanism of action of aCL remains unknown. Human activated protein C functions as a potent anticoagulant in human plasma by inhibiting the activity of coagulation cofactors Va and VIIIa. The purpose of the present study was to investigate the effect of serum IgG fraction obtained from ischemic stroke patients on the rate of protein C activation in cultured human endothelial cells from the umbilical cord veins.
SUBJECTS AND METHODS : The rate of protein C activation was examined in the following groups. We had 10 ischemic stroke patients with positive IgG aCL.These comprised 7 patients with cerebral infarction related SLE (Group 1) and 3 patients without an immunological background including SLE (Group 2). We also examined in 6
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non-SLE related ischemic stroke patients without aCL (Group 3), 14 SLE patients with aCL who did not develop ischemic stroke (Group 4), 6 SLE patients without stroke and aCL (Group 5) and 6 normal controls (Group 6). Confluent endothelial cells were incubated with buffer or IgG obtained from the patients (7 mg/ml) for 1 hour at 37ﾟC.Purified human protein C (1 nM/well) and thrombin (0.04 nM/well) were added. After 2 hours incubation at 37ﾟC,the rate of protein C activation was determined by amidolytic assay employing P-Glu-Pro-Arg-MNA as a substrate. The degree of activation of protein C was expressed as the percent change in the measured absorbance between the presence and absence of the IgG fraction. A negative percent change indicated inhibition of protein C activation.
RESULTS : In SLE related ischemic stroke with positive aCL (Group 1), 5 of the 7 patients revealed a negative percent change which indicated inhibition of the rate of protein C activation by addition of the IgG fraction. The mean percent change of absorbance in these 7 patients was -7.2% (range, from -21.4% to+4.5%). In the 3 non-SLE stroke patients with positive aCL (Group 2), the percent changes in absorbance were -2.0%, -9.8% and -6.6%, respectively. On the other hand, IgG fraction did not appreciably influence the activation of protein C in the patients of Group 3 (the mean parcent change of absorbance, +0.1%), Group 4 (-0.5%) and Group 5 (+0.3%). In the normal controls, the mean percent change in the measured absorbance was +0.6%.
CONCLUSION : Our results appear to indicate that aCL in IgG fractions can interfere with interactions among thrombin, protein C and thrombomodulin on the surface of endothelial cells. Impairment of the rate of activation of protein C could play a role in the development of ischemic stroke. Less
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