FN3K expression in COPD: a potential comorbidity factor for cardiovascular disease

BMJ Open Respir Res. 2020 Nov;7(1):e000714. doi: 10.1136/bmjresp-2020-000714.


Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Keywords: COPD ÀÜ mechanisms; systemic disease and lungs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / genetics
  • Comorbidity
  • Humans
  • Phosphotransferases (Alcohol Group Acceptor)
  • Pilot Projects
  • Pulmonary Disease, Chronic Obstructive* / epidemiology
  • Pulmonary Disease, Chronic Obstructive* / genetics


  • Phosphotransferases (Alcohol Group Acceptor)
  • fructosamine-3-kinase