Molecular variants of soluble guanylyl cyclase affecting cardiovascular risk

Circ J. 2015;79(3):463-9. doi: 10.1253/circj.CJ-15-0025. Epub 2015 Feb 6.


Soluble guanylyl cyclase (sGC) is the physiological receptor for nitric oxide (NO) and NO-releasing drugs, and is a key enzyme in several cardiovascular signaling pathways. Its activation induces the synthesis of the second messenger cGMP. cGMP regulates the activity of various downstream proteins, including cGMP-dependent protein kinase G, cGMP-dependent phosphodiesterases and cyclic nucleotide gated ion channels leading to vascular relaxation, inhibition of platelet aggregation, and modified neurotransmission. Diminished sGC function contributes to a number of disorders, including cardiovascular diseases. Knowledge of its regulation is a prerequisite for understanding the pathophysiology of deficient sGC signaling. In this review we consolidate the available information on sGC signaling, including the molecular biology and genetics of sGC transcription, translation and function, including the effect of rare variants, and present possible new targets for the development of personalized medicine in vascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / enzymology*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / pathology
  • Cyclic GMP / genetics
  • Cyclic GMP / metabolism*
  • Cyclic GMP-Dependent Protein Kinases / genetics
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Guanylate Cyclase / genetics
  • Guanylate Cyclase / metabolism*
  • Humans
  • Ion Channel Gating*
  • Nitric Oxide / genetics
  • Nitric Oxide / metabolism*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Soluble Guanylyl Cyclase


  • Receptors, Cytoplasmic and Nuclear
  • Nitric Oxide
  • Cyclic GMP-Dependent Protein Kinases
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • Cyclic GMP