FN3K expression in COPD: a potential comorbidity factor for cardiovascular disease.
COPD ÀÜ mechanisms
systemic disease and lungs
Journal
BMJ open respiratory research
ISSN: 2052-4439
Titre abrégé: BMJ Open Respir Res
Pays: England
ID NLM: 101638061
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
13
07
2020
revised:
21
10
2020
accepted:
23
10
2020
entrez:
19
11
2020
pubmed:
20
11
2020
medline:
27
10
2021
Statut:
ppublish
Résumé
Cigarette smoking and oxidative stress are common risk factors for the multi-morbidities associated with chronic obstructive pulmonary disease (COPD). Elevated levels of advanced glycation endproducts (AGE) increase the risk of cardiovascular disease (CVD) comorbidity and mortality. The enzyme fructosamine-3-kinase (FN3K) reduces this risk by lowering AGE levels. The distribution and expression of FN3K protein in lung tissues from stable COPD and control subjects, as well as an animal model of COPD, was assessed by immunohistochemistry. Serum FN3K protein and AGE levels were assessed by ELISA in patients with COPD exacerbations receiving metformin. Genetic variants within the FN3K and FN3K-RP genes were evaluated for associations with cardiorespiratory function in the Subpopulations and Intermediate Outcome Measures in COPD Study cohort. This pilot study demonstrates that FN3K expression in the blood and human lung epithelium is distributed at either high or low levels irrespective of disease status. The percentage of lung epithelial cells expressing FN3K was higher in control smokers with normal lung function, but this induction was not observed in COPD patients nor in a smoking model of COPD. The top five nominal FN3K polymorphisms with possible association to decreased cardiorespiratory function (p<0.008-0.02), all failed to reach the threshold (p<0.0028) to be considered highly significant following multi-comparison analysis. Metformin enhanced systemic levels of FN3K in COPD subjects independent of their high-expression or low-expression status. The data highlight that low and high FN3K expressors exist within our study cohort and metformin induces FN3K levels, highlighting a potential mechanism to reduce the risk of CVD comorbidity and mortality.
Identifiants
pubmed: 33208304
pii: 7/1/e000714
doi: 10.1136/bmjresp-2020-000714
pmc: PMC7677354
pii:
doi:
Substances chimiques
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
fructosamine-3-kinase
EC 2.7.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CSRD VA
ID : I01 CX000911
Pays : United States
Organisme : Medical Research Council
ID : MR/T010371/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : U01 HL137880
Pays : United States
Organisme : Wellcome Trust
ID : 093080/Z/10/Z
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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