ArticleAmerican journal of respiratory cell and molecular biology2018
Nitric Oxide-Independent Soluble Guanylate Cyclase Activation Improves Vascular Function and Cardiac Remodeling in Sickle Cell Disease.
Article in American journal of respiratory cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial.The Lancet. Haematology · 2024Trial
- Antibody-Dependent and Antibody-Independent Hemolysis in Sickle Cell Disease.Antibodies (Basel, Switzerland) · 2026Review
- Targeting the NO-cGMP axis in age-related vascular dysfunction: a systematic review and meta-analysis of preclinical animal studies.GeroScience · 2026Review
- Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.EBioMedicine · 2026Review
- Purine Nucleoside Phosphorylase Inhibition Rebalances Purine Metabolism and Attenuates Organ Damage in Sickle Cell Mice.Journal of cellular and molecular medicine · 2025Article
- CYB5R3 T117S tempers fetal hemoglobin induction by hydroxyurea in patients with sickle cell disease.Blood advances · 2024Article
- Soluble guanylate cyclase stimulators and activators: new horizons in the treatment of priapism associated with sickle cell disease.Frontiers in pharmacology · 2024Review
- In vivo noninvasive systemic myography of acute systemic vasoactivity in female pregnant mice.Nature communications · 2023Article
- CYB5R3 in type II alveolar epithelial cells protects against lung fibrosis by suppressing TGF-β1 signaling.JCI insight · 2023Article
- The Role of Inflammation in The Cellular and Molecular Mechanisms of Cardiopulmonary Complications of Sickle Cell Disease.Biomolecules · 2023Review
- A review of cardio-pulmonary microvascular dysfunction in pulmonary hypertension.American heart journal plus : cardiology research and practice · 2023Article
- Increasing nitric oxide bioavailability fails to improve collateral vessel formation in humanized sickle cell mice.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Multiple inducers of endothelial NOS (eNOS) dysfunction in sickle cell disease.American journal of hematology · 2021Review
- Redox Switches Controlling Nitric Oxide Signaling in the Resistance Vasculature and Implications for Blood Pressure Regulation: Mid-Career Award for Research Excellence 2020.Hypertension (Dallas, Tex. : 1979) · 2021Review
- Soluble Guanylate Cyclase Stimulators and Activators.Handbook of experimental pharmacology · 2021Article
- Sickle cell disease: at the crossroads of pulmonary hypertension and diastolic heart failure.Heart (British Cardiac Society) · 2020Review
- Sickle cell disease subjects and mouse models have elevated nitrite and cGMP levels in blood compartments.Nitric oxide : biology and chemistry · 2020Article
- Smooth muscle cytochrome b5 reductase 3 deficiency accelerates pulmonary hypertension development in sickle cell mice.Blood advances · 2019Article
- cGMP modulation therapeutics for sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- New insights into the pathophysiology and development of novel therapies for sickle cell disease.Hematology. American Society of Hematology. Education Program · 2018Review
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22 authors at 7 institutions in 3 countries.
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Abstract
Sickle cell disease (SCD) is associated with intravascular hemolysis and oxidative inhibition of nitric oxide (NO) signaling. BAY 54-6544 is a small-molecule activator of oxidized soluble guanylate cyclase (sGC), which, unlike endogenous NO and the sGC stimulator, BAY 41-8543, preferentially binds and activates heme-free, NO-insensitive sGC to restore enzymatic cGMP production. We tested orally delivered sGC activator, BAY 54-6544 (17 mg/kg/d), sGC stimulator, BAY 41-8543, sildenafil, and placebo for 4-12 weeks in the Berkeley transgenic mouse model of SCD (BERK-SCD) and their hemizygous (Hemi) littermate controls (BERK-Hemi). Right ventricular (RV) maximum systolic pressure (RVmaxSP) was measured using micro right-heart catheterization. RV hypertrophy (RVH) was determined using Fulton's index and RV corrected weight (ratio of RV to tibia). Pulmonary artery vasoreactivity was tested for endothelium-dependent and -independent vessel relaxation. Right-heart catheterization revealed higher RVmaxSP and RVH in BERK-SCD versus BERK-Hemi, which worsened with age. Treatment with the sGC activator more effectively lowered RVmaxSP and RVH, with 90-day treatment delivering superior results, when compared with other treatments and placebo groups. In myography experiments, acetylcholine-induced (endothelium-dependent) and sodium-nitroprusside-induced (endothelium-independent NO donor) relaxation of the pulmonary artery harvested from placebo-treated BERK-SCD was impaired relative to BERK-Hemi but improved after therapy with sGC activator. By contrast, no significant effect for sGC stimulator or sildenafil was observed in BERK-SCD. These findings suggest that sGC is oxidized in the pulmonary arteries of transgenic SCD mice, leading to blunted responses to NO, and that the sGC activator, BAY 54-6544, may represent a novel therapy for SCD-associated pulmonary arterial hypertension and cardiac remodeling.
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