Fig. 2. Carvedilol-mediated β-arrestin biased signaling on β1-adrenergic receptors in cardiomyocytes and hearts. Carvedilol selectively stimulates GRK5/6- and β-arrestin-dependent cardioprotective signaling without activating deleterious G protein signaling. Carvedilol-mediated GRK5/6 phosphorylation of β1-adrenergic receptors leads to β-arrestin1’s translocation into nucleus where β-arrestin1 interacts with a subset of primary miRs and components of the Drosha microprocessor complex. This results in an increased level of a subset of miRs, which act as cardioprotective miRs by repressing pro-apoptotic genes in cardiomyocytes and hearts.
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