Cadherin 11 in calcific aortic valve disease

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.