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Examining the Role of Cytoskeletal Signaling in Cardiac Preconditioning
Author(s) -
Perricone Adam Joseph,
Bivona Benjamin J.,
Jackson Fannie R.,
Vander Heide Richard S.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1085.16
Subject(s) - focal adhesion , cardioprotection , chemistry , myocyte , signal transduction , medicine , ischemia , western blot , endocrinology , biochemistry , gene
Our lab has shown the importance of a cytoskeletal‐based signaling pathway (C‐BSP) in cardiac injury. This study hypothesized that a C‐BSP is necessary for ischemic preconditioning‐(IP) induced cardioprotection (CP). To test this hypothesis, the proximal C‐BSP member focal adhesion kinase (FAK) was selectively knocked out in adult murine ventricular myocytes using an inducible, Cre‐lox system ( Myh6 ‐MCM). All mice underwent 40 min ischemia/24 hr reperfusion (IR). IP was induced using a standard protocol (3×5′+5′ cycles of IR). Control groups included wild type control (C) and tamoxifen‐treated Myh6 ‐MCM +/− ‐flox − (eC). Infarct size (IS) was expressed as a percentage of the LV risk region. IP significantly reduced IS in both C and eC mice (17% vs. 37%; n=8 both groups; P<0.001; 15% vs. 39%; n=7–8; P<0.001, respectively). In FAK KO mice, myocyte FAK levels by Western blot were reduced by 65% compared to C mice (n=3–4; P<0.001), and IS was significantly larger than in C and eC mice (KO 59% vs. 37/39%; n=2–8; P<0.01) indicating that loss of FAK adversely effects myocyte survival in IR. Furthermore, the CP effect of IP was abolished in FAK KO mice (43% vs. 39%; n=3–8; FAK KO vs.eC; P=NS). In summary, abrogation of a key proximal member of the C‐BSP (FAK) results in larger IS in C mice and abolishes IP‐induced CP. We conclude that the C‐BSP plays an important role in myocyte survival in IR injury. Supported by NIH RO1 HL‐084405 to RVH.