FIGURE 2.

Role of the endothelium in cardioprotection. Ischemia/reperfusion injury is associated with increased reactive oxygen species production and Ca²⁺ overload, which ultimately leads to cell death (blue diagram). The endothelium has been described to both precipitate and limit ischemia/reperfusion injury, depending on the physiological state of endothelial cells and/or external stimuli. On the one hand, a healthy endothelium regulates vascular homeostasis, and the production of nitric oxide has been shown to be a key component of remote ischemic preconditioning, as well as to directly reduce ischemia/reperfusion injury by nitrosylating proteins or activating cGMP dependent kinase (green diagram). On the other hand, a dysfunctional endothelium is associated with impaired nitric oxide production, increased vasoconstriction, and reactive oxygen species production, as well as the development of a pro-inflammatory and thrombogenic state, thus favoring the onset of ischemia/reperfusion injury (red diagram). ROS: reactive oxygen species, NO: nitric oxide, RIPC: remote ischemia preconditioning.