Mechanisms leading to calcification of the aortic valve are unclear. Dipeptidyl peptidase 4 (DPP4), an enzyme involved in glucose metabolism, might contribute to this process, according to a new study. In human, cultured valvular interstitial cells (VICs), activation of nuclear factor-κB induced the expression of DPP4, which then promoted osteogenic differentiation through inhibition of insulin-like growth factor 1 (IGF1) signalling. Inhibition of DPP4 blocked in vitro VIC osteogenic differentiation and in vivo aortic valve calcification in Nos3−/− mice. In a rabbit model of calcific aortic valve disease, administration of the DPP4 inhibitor sitagliptin improved clinical parameters, reduced calcium deposits in aortic valve cusps, and increased IGF1 levels in plasma.
References
Choi, B. et al. Dipeptidyl peptidase-4 induces aortic valve calcification by inhibiting insulin-like growth factor-1 signaling in valvular interstitial cells. Circulation http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024270 (2017)
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Fernández-Ruiz, I. DPP4 inhibitors to prevent aortic valve calcification. Nat Rev Cardiol 14, 190 (2017). https://doi.org/10.1038/nrcardio.2017.28
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DOI: https://doi.org/10.1038/nrcardio.2017.28