Figure 3.

Proposed mechanisms of apelin-induced positive inotropy and apelin-independent stretch-induced hypertrophy. (A) Apelin activates apelin receptors on cardiomyocytes to induce positive inotropy. (B) The apelin receptor mediates β-arrestin-dependent signalling (orange) to cause hypertrophy in response to stretch, whereas apelin-activated G_αi signalling (black) is protective. The apelin receptor is represented by the cell surface seven-transmembrane receptor in red; broken arrows indicate unspecified intermediate steps; broken arrow with? mark indicates unknown intermediate steps; + and − signs indicate positive and negative regulation, respectively. Abbreviations: β-arr, β-arrestin; ERK1/2, extracellular signal-regulated kinase 1/2; IP₃, inositol trisphosphate; MEK1/2, mitogen-activated protein kinase kinases 1/2; MLC, myosin light chain; MLCK, myosin light chain kinase; NCX, Na⁺/Ca²⁺ exchanger; NHE1, Na⁺/H⁺ exchanger 1; PKCɛ, protein kinase Cɛ; PLC, phospholipase C; SR, sarcoplasmic reticulum.