**4.10 Cyclic guanosine monophosphate**

Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from GTP (guanosine triphosphate) that acts as a second messenger for activation of intracellular protein kinases in response to the binding of membrane-impermeable hormones to the cell membrane [126]. The important components of cGMP signaling include cGMP-dependent protein kinase G (PKG), ANP, BNP, natriuretic peptide receptor A and C (NPR-A and NPR-C, respectively), neprilysin, NOS3, soluble guanylyl cyclase (sGC), and PDE5 [127]. The cGMP-PKG cascade can decrease the level of calcium and alter the expression of glycoprotein IIb/IIIa. Both fluctuations impact the aggregation of platelets within the body [128]. cGMP levels were found to be higher in patients with implanted VAD compared to healthy individuals. According to Grosman-Rimon *et al.*, cGMP was associated with an elevated risk of gastrointestinal (GI) bleeding during LVAD support [128]. The researchers presume that the association between elevated GI bleeding and higher cGMP levels could be due to platelet abnormalities. The study also found significant alterations of the cGMP-PKG pathway (downregulation of ANP, NPR-C, and cGMP) in patients with dilated cardiomyopathy after VAD implant, while the duration of VAD support negatively correlated with expression differences of PKG I, PDE5, and sGC in patients with ischemic cardiomyopathy.
