Send to:

Choose Destination
See comment in PubMed Commons below
Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2702-10. doi: 10.1161/ATVBAHA.112.300115. Epub 2012 Aug 23.

Decreased Krev interaction-trapped 1 expression leads to increased vascular permeability and modifies inflammatory responses in vivo.

Author information

  • 1University of Rochester, Department of Pharmacology and Physiology, 601 Elmwood Ave, Box 711, Rochester, NY 14642, USA.



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.


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.


Taken together, our data indicate an integral role for KRIT1 in microvessel homeostasis and the vascular response to inflammation.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk