A significance of integrated stress response in the heart

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We created and analyzed αMHC-Fv2E-PERK mice(an inducible eIF2α activator mice) and α MHC-Gadd34C mice(a loss of function model of eIF2α). Notably, the strong activation of eIF2αtriggered by dimerization of PERK transiently suppressed left ventricular systolic function. Left ventricular systolic function was gradually recovered in survivor mice. The strong activation of eIF2α was observed in the severe ischemia. Therefore, we hypothesized that the transient impairment of left ventricular systolic function is resemble to stunned myocardium. We are currently investigating the underlying mechanism of the transient impairment of left ventricular systolic function.