Transglutaminase inhibitors attenuate vascular calcification in a preclinical model.

ABSTRACT:

Objective

In vitro, transglutaminase-2 (TG2)-mediated activation of the β-catenin signaling pathway is central in warfarin-induced calcification, warranting inquiry into the importance of this signaling axis as a target for preventive therapy of vascular calcification in vivo.

Methods and results

The adverse effects of warfarin-induced elastocalcinosis in a rat model include calcification of the aortic media, loss of the cellular component in the vessel wall, and isolated systolic hypertension, associated with accumulation and activation of TG2 and activation of β-catenin signaling. These effects of warfarin can be completely reversed by intraperitoneal administration of the TG2-specific inhibitor KCC-009 or dietary supplementation with the bioflavonoid quercetin, known to i

SUBMITTER: Beazley KE 

PROVIDER: S-EPMC3544469 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature