Figure 2.

(A) Two pathways of [Ca²⁺]_i influencing VSMC stiffness and adhesion properties in VSMCs. [Ca²⁺]_i-induced α-SMA and α5β1 integrin expressions for regulating VSMC stiffness and adhesion (red line) via ECM-integrin-cytoskeletal axis is parallel to the Ca²⁺-CaM-MLCK pathway in VSMCs (black line). All abbreviations in figure: [Ca²⁺]_i, Intercellular Ca²⁺ concentration; ANG II, Angiotensin II; GPCR, G-protein-coupled receptor; G_q, Guanine nucleotide-binding protein; GDP, Guanosine diphosphate; GTP, Guanosine triphosphate; G_α, G protein α subunit; PLC, Phospholipase C; PIP₂, Phosphatidylinositol 4,5-bisphosphate; IP₃, Inositol trisphosphate; DAG, Diacylglycerol; SR, Sarcoplasmic reticulum; PKC, Protein kinase C; LTCC, L-type Ca²⁺ channel; CaM, Calmodulin; CaMKII, CaM-dependent protein kinase II; MLCK, Myosin light chain kinase; pMLCK, Phosphorylated myosin light chain kinase; MLC, Myosin light chain; pMLC, Myosin light chain phosphatase; α-SMA, α-smooth muscle actin; FAK, Focal adhesion kinase. (B) The new concept of [Ca²⁺]_i influencing VSMC stiffness and adhesion properties via ECM-integrin-cytoskeletal axis. [Ca²⁺]_i directly manipulates the expressions of α-SMA and α5β1 integrin, and the α5β1 integrin regulates [Ca²⁺]_i level in accordance with physiological requirement.