Idiopathic calcific aortic valve disease (CAVD) has been associated with silencing of the NOTCH1 gene. Valve interstitial cells from Notch1+/− mice have been shown to overexpress cadherin 11, a cell junction protein. To determine whether targeting cadherin 11 can prevent CAVD in Notch1+/− mice, Clark and colleagues administered either 10 mg/kg of SYN0012 (a cadherin 11-blocking antibody) or an IgG2a isotype control to Notch1+/+ and Notch1+/− mice. Notch1+/− mice that received IgG2a had decreased ejection fraction velocity ratio compared with SYN0012-treated mice. On histology, SYN0012-treated Notch1+/− mice had thin leaflets (indicating healthy valve morphology), whereas mice that received IgG2a had hyperplastic leaflets with calcified regions. In addition, expression of IL-6, an inflammatory cytokine, was upregulated in leaflets from mice that received IgG2a compared with leaflets from SYN0012-treated mice. Together, these observations show that blocking cadherin 11 expression can prevent the pathological phenotype seen in Notch1+/− mice.
References
Clark, C. R. et al. Targeting cadherin-11 prevents Notch1-mediated calcific aortic valve disease. Circulation http://dx.doi.org/10.1161/CIRCULATIONAHA.117.027771 (2017)
Rights and permissions
About this article
Cite this article
Huynh, K. Cadherin 11 in calcific aortic valve disease. Nat Rev Cardiol 14, 442 (2017). https://doi.org/10.1038/nrcardio.2017.99
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrcardio.2017.99