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Current Pharmaceutical Design
ISSN (Print): 1381-6128
ISSN (Online): 1873-4286
Epub Abstract Ahead of Print
DOI: 10.2174/1381612820666140212205059      Price:  $95

New Therapeutic Approaches to Arterial Calcification Via Inhibition of Transglutaminase and B-Catenin Signaling

Author(s): Mikhail Konoplyannikov and Maria Nurminskaya
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Arterial calcification (AC) is a hallmark of many serious diseases, including atherosclerosis, chronic kidney disease, and diabetes. AC may also develop as a side-effect of therapy with anticoagulants, such as warfarin which is widely used for prophylaxis of thrombosis. In our studies, we established the relation between warfarin-induced AC and activation of enzyme transglutaminase 2 (TG2) and β-catenin signaling. We showed that TG2-specific inhibitor KCC-009 significantly attenuated the damaging effects of warfarin on arterial tissue. A similar protective effect was also achieved with a dietary bioflavonoid quercetin that inhibits TG2 and β-catenin signaling. We have shown that quercetin intercepts the chondrogenic transformation of vascular smooth muscle and also drastically attenuates calcifying cartilaginous metaplasia in another model of AC caused by genetic loss of matrix gla protein (MGP). These findings suggest that quercetin may be considered as a promising anti-AC therapeutic in the clinical settings of warfarin supplementation and MGP dysfunction. Further studies are required to test the efficacy of quercetin on other types of AC
Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore. Maryland, USA