| First Author | Perricone AJ | Year | 2013 |
| Journal | J Am Heart Assoc | Volume | 2 |
| Issue | 5 | Pages | e000457 |
| PubMed ID | 24080910 | Mgi Jnum | J:202456 |
| Mgi Id | MGI:5519145 | Doi | 10.1161/JAHA.113.000457 |
| Citation | Perricone AJ, et al. (2013) Conditional knockout of myocyte focal adhesion kinase abrogates ischemic preconditioning in adult murine hearts. J Am Heart Assoc 2(5):e000457 |
| abstractText | BACKGROUND: Our laboratory has previously demonstrated the importance of a cytoskeletal-based survival signaling pathway using in vitro models of ischemia/reperfusion (IR). However, the importance of this pathway in mediating stress-elicited survival signaling in vivo is unknown. METHODS AND RESULTS: The essential cytoskeletal signaling pathway member focal adhesion kinase (FAK) was selectively deleted in adult cardiac myocytes using a tamoxifen-inducible Cre-Lox system (alpha-MHC-MerCreMer). Polymerase chain reaction (PCR) and Western blot were performed to confirm FAK knockout (KO). All mice were subjected to a 40-minute coronary occlusion followed by 24 hours of reperfusion. Ischemic preconditioning (IP) was performed using a standard protocol. Control groups included wild-type (WT) and tamoxifen-treated alpha-MHC-MerCreMer+/-/FAK(WT/WT) (experimental control) mice. Infarct size was expressed as a percentage of the risk region. In WT mice IP significantly enhanced the expression of activated/phosphorylated FAK by 36.3% compared to WT mice subjected to a sham experimental protocol (P </= 0.05; n = 6 hearts [sham], n = 4 hearts [IP]). IP significantly reduced infarct size in both WT and experimental control mice (43.7% versus 19.8%; P </= 0.001; 44.7% versus 17.5%; P </= 0.001, respectively). No difference in infarct size was observed between preconditioned FAK KO and nonpreconditioned controls (37.1% versus 43.7% versus 44.7%; FAK KO versus WT versus experimental control; P=NS). IP elicited a 67.2%/88.8% increase in activated phosphatidylinositol-3-kinase (PI3K) p85/activated Akt expression in WT mice, but failed to enhance the expression of either in preconditioned FAK KO mice. CONCLUSIONS: Our results indicate that FAK is an essential mediator of IP-elicited cardioprotection and provide further support for the hypothesis that cytoskeletal-based signaling is an important component of stress-elicited survival signaling. |
