Figure 1.

Role of ECS in cardiovascular injury/disease. Cardiovascular insult inflicted by ischemia, inflammation or hemodynamic overload leads to increased formation of reactive oxygen and/or nitrogen species (ROS/RNS) and inflammation. These processes trigger activation of ECS in cardiovascular system and infiltrating immune cells. eCBs via activation of CB₁ in cardiomyocytes, endothelial cells, fibroblasts and certain immune cells promote processes facilitating development of cardiovascular dysfunction, inflammation and pathological remodeling. In contrast, eCBs via activation of CB₂ exert opposing protective effects. Moreover, eCBs through their catabolism by FAAH and/or MAGL or oxidation by cyclooxygenases (COXs) or other enzymes may represent a significant source of arachidonic acid (AA) and/or other oxidized eCB metabolites with both pro- and anti-inflammatory effects. Thus, the protective or detrimental effect of eCBs in cardiovascular diseases may largely be context-, time- and pathology-dependent.