Acute Tetrahydrobiopterin Improves Endothelial Function in Patients With COPD

Autor: Ryan A. Harris, Thomas A. Dillard, Justin Gregg, Jennifer C. Sullivan, Jeffrey Thomas, Nichole Seigler, Jennifer S. Pollock, Paula Rodriguez-Miguelez, Leon Bass
Rok vydání: 2018
Předmět:
Pulmonary and Respiratory Medicine
Male
medicine.medical_specialty
Blotting
Western
Regulator
Administration
Oral
Enzyme-Linked Immunosorbent Assay
030204 cardiovascular system & hematology
Critical Care and Intensive Care Medicine
Placebo
Nitric Oxide
Gastroenterology
Nitric oxide
03 medical and health sciences
chemistry.chemical_compound
Pulmonary Disease
Chronic Obstructive
0302 clinical medicine
Double-Blind Method
Internal medicine
medicine
Humans
Endothelial dysfunction
Aorta
Cells
Cultured
COPD
Cross-Over Studies
business.industry
Tetrahydrobiopterin
Middle Aged
medicine.disease
Endothelin 1
Crossover study
Biopterin
Treatment Outcome
030228 respiratory system
chemistry
Female
Endothelium
Vascular
Nitric Oxide Synthase
Cardiology and Cardiovascular Medicine
business
Biomarkers
medicine.drug
Zdroj: Chest. 154(3)
ISSN: 1931-3543
Popis: Background Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH4 would improve endothelial function in patients with COPD via an increase in NO bioavailability. Methods Seventeen patients with COPD completed a randomized, double-blind, placebo (PLC)-controlled, crossover trial with an acute dose of either BH4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC. Flow-mediated dilation (FMD), a bioassay of endothelial function, was completed prior to and 3 h following each treatment. Phospho- and total endothelial NO synthase (NOS3) protein was evaluated after incubating endothelial cells with plasma from the patients prior to and following treatment. Fifteen demographically matched control subjects were tested at baseline for case control comparisons. Results Treatment with BH4 significantly (P ≤ .004) increased FMD, improving endothelial function in patients compared to control values (P ≥ .327). BH4 increased (P = .013) the ratio of phospho-NOS3 to total NOS3 protein. No changes in FMD (P ≥ .776) or the protein ratio (P = .536) were observed following PLC. Conclusions An acute dose of BH4 was able to improve endothelial function in patients with COPD to values similar to control subjects. The improvement in endothelial function was accompanied by an increase in NOS3 phosphorylation. BH4 may represent a potential novel therapy to improve endothelial function and reduce cardiovascular disease risk in patients with COPD. Trial Registry ClinicalTrials.gov; No.: NCT01398943; URL: www.clinicaltrials.gov.
Databáze: OpenAIRE
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