“…Moreover, compared to LA tissue, RA tissue exhibits higher estrogen receptor-α expression, which is constitutionally expressed on cardiac fibroblasts and may inhibit the profibrotic cellular activities of cardiac fibroblasts through the modulation of Ca 2+ homeostasis [ 64 , 67 , 68 , 108 , 109 , 110 ]. In our previous study, we identified the diverse protein expression in transient receptor potential (TRP) channels, phosphorylated phospholipase C (PLC), and the stromal interaction molecule (STIM)1 between LA and RA fibroblasts [ 59 ]. Phospholipase C (PLC), the second messenger of multiple profibrotic cytokines [ 111 , 112 ], hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2), thereby producing diacylglycerol (DAG) and inositol trisphosphate (IP3).…”