Figure 2.

ROS activates TRPC3/TRPC4 heterotetramers and TRPV4 in vascular endothelial cells. ROS may activate endothelial TRPC3/TRPC4 heterotetramers and TRPV4 by exploiting two distinct mechanisms. ROS could stimulate PLCγ1 to cleave DAG from the minor membrane phospholipide, PIP₂, thereby gating the TRPC3/TRPC4 heterotetramer. ROS could be detected by Fyn, which is required to activate TRPV4 in a redox-sensitive manner. The physical association between Fyn and TRPV4 is maintained by CD36. Laminar shear stress may boost the mitochondrial production of ROS by stimulating TRPV4-mediated extracellular Ca²⁺ entry.