Life-threatening hemorrhage and prolonged wound healing are remarkable phenotypes manifested by complete plasminogen activator inhibitor-1 deficiency in humans.
J Thromb Haemost
; 9(6): 1200-6, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21486382
ABSTRACT
BACKGROUND:
Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological regulator of urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA) activity. A number of studies have shown that elevated levels of PAI-1 are related to pathological states such as an increased risk of arterial thrombotic events and a poor prognosis for cancer patients; however, there are few reports about PAI-1 deficiency in humans because the disorder is very rare.OBJECTIVE:
To understand the in vivo impact of a complete PAI-1 deficiency, Serpine1(-/-) mice were generated; a number of in vivo studies have been conducted to elucidate the function of PAI-1 using Serpine1(-/-) mice. The phenotypes demonstrated in Serpine1(-/-) mice, however, were quite different from those in humans. Therefore, it is necessary to find out and analyze SERPINE1 deficiency in humans. PATIENT ANDMETHODS:
The patient is a 47-year-old woman who has had multiple episodes of major bleeding. Although most of the patient's blood coagulation factors were functionally normal, her PAI-1 antigen levels were undetectable. Therefore, DNA sequencing of the SERPINE1 gene were analyzed.RESULTS:
The proband had a homozygous 1-bp duplication (C) at exon 3 (c.356dupC; p.Ile120AspfsX42). Both wild-type PAI-1 (42.7 kDa) and mutated (Mut) PAI-1 (14.7kDa) were expressed in COS-1 cells, although the level of Mut PAI-1 expressed in the cell lysates was much lower. Wild-type PAI-1 was observed in the culture supernatant, whereas no Mut PAI-1 was detected in the supernatant.CONCLUSIONS:
Considering the results of the present study, the translation of mouse studies to humans must be performed with great care.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cicatrização
/
Inibidor 1 de Ativador de Plasminogênio
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Serpina E2
/
Hemorragia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Thromb Haemost
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Japão