Fig. 8.
Schematic of α1A-AR–mediated cardiac hypertrophy and antagonistic hypertrophic signaling initiated with coactivation with the α1B-AR. α1A-ARs mediate the secretion of IL-6 into the bloodstream from various cell types such as myocytes, vascular smooth muscle cells, fibroblasts, lymphocytes, and endothelial cells. The secreted IL-6 acts on the myocyte to mediate cardiac hypertrophy through STAT3 nuclear signaling. α1A-ARs also phosphorylate STAT3 independent of IL-6 secretion. α1B-ARs mediate hypertrophic NF-κB signaling. When α1A- and α1B-ARs are coexpressed and coactivated, hypertrophic signals through p38, NK-κB, and STAT3 are inhibited. Inhibition of both p38 and NF-κB downregulate the expression and secretion of IL-6 from the myocyte.