Chapter title |
Novel sGC Stimulators and sGC Activators for the Treatment of Heart Failure
|
---|---|
Chapter number | 100 |
Book title |
Heart Failure
|
Published in |
Handbook of experimental pharmacology, January 2016
|
DOI | 10.1007/164_2016_100 |
Pubmed ID | |
Book ISBNs |
978-3-31-959658-7, 978-3-31-959659-4
|
Authors |
Stefanie Breitenstein, Lothar Roessig, Peter Sandner, Kelly S. Lewis |
Abstract |
The burden of heart failure (HF) increases worldwide with an aging population, and there is a high unmet medical need in both, heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). The nitric oxide (NO) pathway is a key regulator in the cardiovascular system and modulates vascular tone and myocardial performance. Disruption of the NO-cyclic guanosine monophosphate (cGMP) signaling axis and impaired cGMP formation by endothelial dysfunction could lead to vasotone dysregulation, vascular and ventricular stiffening, fibrosis, and hypertrophy resulting in a decline of heart as well as kidney function. Therefore, the NO-cGMP pathway is a treatment target in heart failure. Exogenous NO donors such as nitrates have long been used for treatment of cardiovascular diseases but turned out to be limited by increased oxidative stress and tolerance. More recently, novel classes of drugs were discovered which enhance cGMP production by targeting the NO receptor soluble guanylate cyclase (sGC). These compounds, the so-called sGC stimulators and sGC activators, are able to increase the enzymatic activity of sGC to generate cGMP independently of NO and have been developed to target this important signaling cascade in the cardiovascular system.This review will focus on the role of sGC in cardiovascular (CV) physiology and disease and the pharmacological potential of sGC stimulators and sGC activators therein. Preclinical data will be reviewed and summarized, and available clinical data with riociguat and vericiguat, novel direct sGC stimulators, will be presented. Vericiguat is currently being studied in a Phase III clinical program for the treatment of heart failure with reduced ejection fraction (HFrEF). |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 56 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 11 | 20% |
Student > Bachelor | 6 | 11% |
Student > Master | 6 | 11% |
Student > Doctoral Student | 3 | 5% |
Other | 3 | 5% |
Other | 5 | 9% |
Unknown | 22 | 39% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 11 | 20% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 14% |
Biochemistry, Genetics and Molecular Biology | 6 | 11% |
Agricultural and Biological Sciences | 3 | 5% |
Nursing and Health Professions | 2 | 4% |
Other | 5 | 9% |
Unknown | 21 | 38% |