@article{39f004beae7147dea2fa620c8d3c5f52,
title = "Soluble guanylate cyclase: A potential therapeutic target for heart failure",
abstract = "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.",
keywords = "Cyclic guanosine monophosphate, Heart failure, Pathophysiology, Soluble guanylate cyclase, Treatment",
author = "Mihai Gheorghiade and Marti, {Catherine N.} and Sabbah, {Hani N.} and Lothar Roessig and Greene, {Stephen J.} and Michael B{\"o}hm and Burnett, {John C.} and Umberto Campia and Cleland, {John G.F.} and Collins, {Sean P.} and Fonarow, {Gregg C.} and Levy, {Phillip D.} and Marco Metra and Bertram Pitt and Piotr Ponikowski and Naoki Sato and Voors, {Adriaan A.} and Stasch, {Johannes Peter} and Javed Butler",
note = "Funding Information: Conflict of interest Mihai Gheorghiade, MD, is consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical, and Trevena Therapeutics. Hani N. Sabbah, PhD, received research grants from Bayer Healthcare and is consultant to Bayer Healthcare. Lothar Roessig, MD, is a full-time employee at Bayer HealthCare AG. Michael B{\"o}hm, MD, was supported by Boehringer-Ingelheim, Servier, Pfizer, and Medtronic. John C. Burnett, MD, received research grant from Bayer. Umberto Campia, MD, was supported by a National Institutes of Health grant (K12-HL083790). John G.F. Cleland, MD, received an honorarium from Bayer for an advisory board. Funding level is modest. Sean P. Collins, MD, MSc, received research grant and support from Abbott Point-of-Care, NIH/NHLBI. Consultation was made with Abbot Point-of-Care, Bayer, Trevena, Novartis, and The Medicines Company. Gregg C. Fonarow, MD, is consultant to Novartis, Medtronic, and Takeda. Phillip D. Levy, MD, MPH, received research grant/support from Corthera, Inc. and Bayer Schering AG; consultant for Corthera, Inc., The Medicines Company, Bayer Schering Pharma AG, Trevena, Inc., and EKR Therapeutics. Marco Metra, MD received honoraria for participation to advisory board meetings or speeches for Bayer, Corthera, and Novartis. Bertram Pitt, MD is consultant to Pfizer, Novartis, Bayer, Merck, Takeda, Astra Zeneca, GE-Healthcare, BG-medicine, and Relypsa. Stock options were made with BG-medicine and Relypsa. Grants were received from Forrest Laboratories and Novartis. Piotr Poni-kowski, MD, PhD, is consultant to Bayer Schering AG, Corthera, Amgen, Johnson&Johnson. Naoki Sato, MD, PhD, is consultant to Chugai Pharmaceutical Company and honoraria from Daiichi-Sankyo, Otsuka, Philips Respironics, Astellas, Ono, Eisai, Chugai, Mitsubishi-Tanabe, Sanofi-Aventis, and Novartis pharmaceuticals. Adriaan A. Voors, MD, PhD, has received consulting fee from Bayer. Johannes-Peter Stasch, PhD, is a full-time employee at Bayer HealthCare AG. Javed Butler, MD, MPH, is consultant to Cardiom-ems, Trevena, Bayer Healthcare, Takeda, and Amgen and associated with Events Committee for WorldHeart and Corthera. Research support was provided by GE Healthcare and Medtronic. Catherine N. Marti, MD, and Stephen J. Greene, MD, did not received any support.",
year = "2013",
month = mar,
doi = "10.1007/s10741-012-9323-1",
language = "English (US)",
volume = "18",
pages = "123--134",
journal = "Heart Failure Reviews",
issn = "1382-4147",
publisher = "Springer Netherlands",
number = "2",
}