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Soluble guanylate cyclase: a potential therapeutic target for heart failure.

Publication ,  Journal Article
Gheorghiade, M; Marti, CN; Sabbah, HN; Roessig, L; Greene, SJ; Böhm, M; Burnett, JC; Campia, U; Cleland, JGF; Collins, SP; Fonarow, GC ...
Published in: Heart Fail Rev
March 2013

The number of annual hospitalizations for heart failure (HF) and the mortality rates among patients hospitalized for HF remains unacceptably high. The search continues for safe and effective agents that improve outcomes when added to standard therapy. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway serves an important physiologic role in both vascular and non-vascular tissues, including regulation of myocardial and renal function, and is disrupted in the setting of HF, leading to decreased protection against myocardial injury, ventricular remodeling, and the cardio-renal syndrome. The impaired NO-sGC-cGMP pathway signaling in HF is secondary to reduced NO bioavailability and an alteration in the redox state of sGC, making it unresponsive to NO. Accordingly, increasing directly the activity of sGC is an attractive pharmacologic strategy. With the development of two novel classes of drugs, sGC stimulators and sGC activators, the hypothesis that restoration of NO-sGC-cGMP signaling is beneficial in HF patients can now be tested. Characterization of these agents in pre-clinical and clinical studies has begun with investigations suggesting both hemodynamic effects and organ-protective properties independent of hemodynamic changes. The latter could prove valuable in long-term low-dose therapy in HF patients. This review will explain the role of the NO-sGC-cGMP pathway in HF pathophysiology and outcomes, data obtained with sGC stimulators and sGC activators in pre-clinical and clinical studies, and a plan for the further clinical development to study these agents as HF therapy.

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Published In

Heart Fail Rev

DOI

EISSN

1573-7322

Publication Date

March 2013

Volume

18

Issue

2

Start / End Page

123 / 134

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Soluble Guanylyl Cyclase
  • Signal Transduction
  • Receptors, Cytoplasmic and Nuclear
  • Nitric Oxide
  • Humans
  • Hemodynamics
  • Heart Failure
  • Guanylate Cyclase
  • Cyclic GMP
 

Citation

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Gheorghiade, M., Marti, C. N., Sabbah, H. N., Roessig, L., Greene, S. J., Böhm, M., … Academic Research Team in Heart Failure (ART-HF), . (2013). Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Fail Rev, 18(2), 123–134. https://doi.org/10.1007/s10741-012-9323-1
Gheorghiade, Mihai, Catherine N. Marti, Hani N. Sabbah, Lothar Roessig, Stephen J. Greene, Michael Böhm, John C. Burnett, et al. “Soluble guanylate cyclase: a potential therapeutic target for heart failure.Heart Fail Rev 18, no. 2 (March 2013): 123–34. https://doi.org/10.1007/s10741-012-9323-1.
Gheorghiade M, Marti CN, Sabbah HN, Roessig L, Greene SJ, Böhm M, et al. Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Fail Rev. 2013 Mar;18(2):123–34.
Gheorghiade, Mihai, et al. “Soluble guanylate cyclase: a potential therapeutic target for heart failure.Heart Fail Rev, vol. 18, no. 2, Mar. 2013, pp. 123–34. Pubmed, doi:10.1007/s10741-012-9323-1.
Gheorghiade M, Marti CN, Sabbah HN, Roessig L, Greene SJ, Böhm M, Burnett JC, Campia U, Cleland JGF, Collins SP, Fonarow GC, Levy PD, Metra M, Pitt B, Ponikowski P, Sato N, Voors AA, Stasch J-P, Butler J, Academic Research Team in Heart Failure (ART-HF). Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Fail Rev. 2013 Mar;18(2):123–134.
Journal cover image

Published In

Heart Fail Rev

DOI

EISSN

1573-7322

Publication Date

March 2013

Volume

18

Issue

2

Start / End Page

123 / 134

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Soluble Guanylyl Cyclase
  • Signal Transduction
  • Receptors, Cytoplasmic and Nuclear
  • Nitric Oxide
  • Humans
  • Hemodynamics
  • Heart Failure
  • Guanylate Cyclase
  • Cyclic GMP