[Background] Cardiomyocyte (CM) death causes CM loss, resulting in heart failure. Therefore, the prevention of CM death could be a novel therapeutic strategy. Previously, we reported that the knockdown of defender against cell death 1(Dad1) induced CM death. However, the detail mechanism and pathological significance of Dad1-mediated cardioprotection are unknown. The aim of this study is to clarify cardioprotective roles of Dad1 in heart.
[Methods/Results] In neonatal rat CMs, the expression of Dad1 was suppressed by using siRNA. Immunoblot showed that N-Cadherin expression and integrinβ1 molecular weight were decreased in Dad1 knock-down CMs. Also, the expression of phosphorylated focal adhesion kinase (pFAK) was decreased and the expression of cleaved caspase3 was increased in Dad1 knock-down CMs. In addition, a cell adhesion enhancer, adhesamine, attenuated CM death, pFAK reduction and caspase3 activation induced by suppression of Dad1. In vivo study, we made cardiomyocyte-specific Dad1 conditional hetero knock-out (CKO) mice by using Cre/loxP system. Phenotypes were no differences between Dad1 CKO mice and control mice, but the expression of N-cadherin and pFAK were decreased in Dad1 CKO mice.
[Conclusion] Dad1 could exhibit cardioprotective properties by maturing cell adhesion in heart.