On the cover: Molecular mechanism of angiotensin receptor type-1 agonistic antibodies (AT₁-AA)-mediated AT₁ receptor activation. Multiple signaling pathways function downstream of AT₁-AA-mediated AT₁ receptor activation. AT₁-AA-mediated AT₁ receptor activation leads to increased protein kinase C (PKC) and calcineurin activity. As a result, downstream transcription factors, such as activating protein-1 (AP-1), nuclear factor κB (NF-κB), and nuclear factor activating T cell (NFAT), are activated and translocated from cytosol to nucleus, which leads to increased gene expression. Because AT₁-activating autoantibodies are bivalent IgG protein complexes, their agonistic effect is proposed to be exerted by cross-linking and thereby stabilizing AT₁ receptor homodimers. DAG indicates diacylglycerol; IP3, inositol triphosphate; PAI-1, plasminogen activating inhibitor-1; and TF, tissue factor. (See page 272.)

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