Thus, it forms a critical feedback loop signaling pathway of β1-AR/cAMP/PKA/GATA-4/let-7/β1-AR, and the decreasing of β1-AR in CIHF is induced by β1-AR activation in early phase of CIHF, which is a kind of self-regulation of β1-AR in the course of ischemia induced heart failure. Here, GATA4 is linked to ischemia.