Decreased Krev interaction-trapped 1 expression leads to increased vascular permeability and modifies inflammatory responses in vivo.
Arterioscler Thromb Vasc Biol
; 32(11): 2702-10, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-22922958
ABSTRACT
OBJECTIVE:
The regulation of vascular permeability, leukocyte trafficking, and the integrity of endothelial cell-cell contacts are closely linked by a complex mechanism of interregulation. Here, we investigate the role of Krev interaction-trapped 1 (KRIT1), an adherens junction accessory protein required for cell-cell junction stability, in regulating these vascular functions. METHODS ANDRESULTS:
Krit1(+/-) mice exhibited an enhanced edematous response to the complex inflammatory stimuli found in the passive K/BxN model of inflammatory arthritis and the murine air pouch model, yet leukocyte infiltration was unchanged. Correspondingly, reduced KRIT1 expression increased baseline arteriole and venule permeability 2-fold over that of wild-type littermates, as measured by intravital microscopy of the intact cremaster muscle vascular network, but this increase was not accompanied by increased leukocyte extravasation or activation. Direct stimulation with tumor necrosis factor-α induced increased permeability in wild-type mice, but surprisingly no increase over baseline levels was observed in Krit1(+/-) mice, despite extensive leukocyte activation. Finally, adoptive transfer of Krit1(+/-) bone marrow failed to increase permeability in wild-type mice. However, reduced expression of KRIT1 in the hematopoietic lineage dampened the differences observed in baseline permeability.CONCLUSIONS:
Taken together, our data indicate an integral role for KRIT1 in microvessel homeostasis and the vascular response to inflammation.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Arteríolas
/
Artrite
/
Vênulas
/
Permeabilidade Capilar
/
Proteínas Proto-Oncogênicas
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Edema
/
Proteínas Associadas aos Microtúbulos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos