Abstract | OBJECTIVE: METHODS AND RESULTS: CONCLUSIONS:
Sildenafil enhances canonical BMP signaling via cyclic GMP and cyclic GMP-dependent protein kinase I in vitro and in vivo, and partly restores deficient BMP signaling in BMPR-II mutant PASMCs. Our findings demonstrate a novel mechanism of action of sildenafil in the treatment of PAH and suggest that targeting BMP signaling may be beneficial in this disease.
|
Authors | Jun Yang, Xiaohui Li, Rafia S Al-Lamki, Changxin Wu, Astrid Weiss, Joachim Berk, Ralph T Schermuly, Nicholas W Morrell |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 33
Issue 1
Pg. 34-42
(Jan 2013)
ISSN: 1524-4636 [Electronic] United States |
PMID | 23139294
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antihypertensive Agents
- Bone Morphogenetic Protein 4
- Bone Morphogenetic Proteins
- ID1 protein, human
- ID1 protein, rat
- Inhibitor of Differentiation Protein 1
- Phosphodiesterase 5 Inhibitors
- Piperazines
- Purines
- SMAD1 protein, human
- SMAD5 protein, human
- Smad1 Protein
- Smad1 protein, rat
- Smad5 Protein
- Smad5 protein, rat
- Sulfones
- Vasodilator Agents
- 8-bromocyclic GMP
- Monocrotaline
- Sildenafil Citrate
- Cyclic GMP-Dependent Protein Kinase Type I
- PRKG1 protein, human
- BMPR2 protein, human
- Bmpr2 protein, rat
- Bone Morphogenetic Protein Receptors, Type II
- Cyclic GMP
|
Topics |
- Animals
- Antihypertensive Agents
(pharmacology)
- Binding Sites
- Bone Morphogenetic Protein 4
(metabolism)
- Bone Morphogenetic Protein Receptors, Type II
(drug effects, genetics, metabolism)
- Bone Morphogenetic Proteins
(metabolism)
- Cell Proliferation
(drug effects)
- Cells, Cultured
- Cyclic GMP
(analogs & derivatives, metabolism, pharmacology)
- Cyclic GMP-Dependent Protein Kinase Type I
(genetics, metabolism)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Familial Primary Pulmonary Hypertension
- Humans
- Hypertension, Pulmonary
(chemically induced, metabolism, prevention & control)
- Inhibitor of Differentiation Protein 1
(genetics, metabolism)
- Male
- Monocrotaline
- Muscle, Smooth, Vascular
(drug effects, metabolism)
- Mutation
- Myocytes, Smooth Muscle
(drug effects, metabolism)
- Phosphodiesterase 5 Inhibitors
(pharmacology)
- Phosphorylation
- Piperazines
(pharmacology)
- Promoter Regions, Genetic
- Pulmonary Artery
(drug effects, metabolism)
- Purines
(pharmacology)
- RNA Interference
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
(drug effects)
- Sildenafil Citrate
- Smad1 Protein
(metabolism)
- Smad5 Protein
(metabolism)
- Sulfones
(pharmacology)
- Transfection
- Vasodilator Agents
(pharmacology)
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|