Figure 3.

Myofibroblast (myoFb) cross-talk with neighboring myocytes via paracrine signaling involving de novo angiotensin (Ang) II generation and AT₁ receptor binding. Ensuing IP₃ stimulation leads to the release from and subsequent fall in endoplasmic reticulum [Ca²⁺]_er whose Ca²⁺ sensor, STIM1, in turn, is then activated to promote store-operated Ca²⁺ channel entry (SOCE) to raise cytosolic [Ca²⁺]_i and mitochondrial [Ca²⁺]_m. Ensuing oxidative stress and reactive oxygen species (ROS) activate proteolytic UPS ligases (MuRF1 and atrogin-1) leading to myocyte protein degradation with resultant atrophy.