Figure 2.

Mitochondrial permeability transition pore (MPTP) opening is the main end effector in ischemia reperfusion injury (IRI). On one side, platelets contribute to IRI mainly by microthrombi formation and platelet-leukocyte aggregates (PLAs). On the other side, molecules of platelet origin, such as platelet activating factor phosphoglyceride (PAF) and sphingosine-1-phosphate (S1P), lead to the activation of cardioprotective pathways, such as the reperfusion injury salvage kinase (RISK) pathway and the survivor activating factor enhancement (SAFE) pathway, all targeting inhibition of MPTP opening. Besides, the interaction between platelets and gasotransmitters has a central role in cardioprotection. Nitric oxide (NO) activates the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) pathway, leading to the inhibition of platelet adhesion, activation, and aggregation. NO can inhibit platelet response also by cGMP-independent mechanisms. NO inhibitory effect on platelets is reduced in the presence of increased levels of reactive oxygen species (ROS). Also, PKG leads to the opening of the mitochondrial ATP-dependent K+ channel (mitoKATP) and subsequent inhibition of MPTP. Carbon monoxide (CO) exerts its cardioprotective action triggering the opening of mitoKATP with consequent inhibition of the opening of MPTP and modulating mitochondrial ROS production. Furthermore, it can inhibit platelet activation both by cGMP-dependent and cGMP-independent mechanisms.