{
  "abstract": "Background Fructosamine-3-Kinase (FN3K) is considered a ‘housekeeping gene’, a crucial enzyme for protein deglycation, mitigating the accumulation of advanced glycation end-products (AGEs) that drive oxidative stress and chronic inflammation. FN3K phosphorylates fructosamines on lysine residues, facilitating AGE removal and preserving protein and mitochondrial function (Delpierre et al., 2000). Reduced FN3K activity leads to mitochondrial dysfunction, a hallmark of cardiovascular disease (CVD) and comorbidities like diabetes and pulmonary fibrosis (Maillard et al., 2019; Semba et al., 2010).Aim To Investigate FN3K expression in vascular cells (AoSMC, AoEC, HUVEC) and its functional impact on mitochondria and pro-fibrotic events.Methods Cells were treated with pro-inflammatory cytokines IL-1β, IL-6, along with negative control. FN3K/FN3K-RP expression was assessed by qPCR. Functional impact of reduced FN3K was evaluated via siRNA knockdown.Results IL-1β transiently increased FN3K in AoSMCs (~1.5–1.6-fold at 30 min) before dropping to ~0.2–0.3 (~70–80%↓) by 24 h. AoECs showed faster suppression (~0.4 by 2 h, sustained to 24 h). HUVECs peaked at 30 min (~4–5-fold) then returned to baseline by 2 h and ~80%↓ at 24 h. FN3K-RP was largely unchanged. IL-6 had minimal effect, fluctuating near baseline. siRNA knockdown achieved ~50–60% FN3K mRNA reduction in AoSMCs, confirming silencing for functional studies.Conclusion Contradictory to current dogma, expression of FN3K is cytokine-responsive in aortic smooth muscle and endothelial cells, resulting in decreased expression upon treatment with IL-1β and partially with IL-6. Furthermore, it has been shown previously by our group that metformin can increase FN3K expression. It is anticipated that continuous localized pro-inflammatory episodes could lead to decreased mitochondrial function and promotion of fibrosis leading to conditions such aortic stenosis. Ongoing investigations are exploring this hypothesis.References Delpierre G, Collard F, Fortpied J, Van Schaftingen E. Fructosamine 3-kinase, an enzyme involved in protein deglycation. Biochemical Journal 2000;350(Pt 1):71–77. Maillard-Leonard F, Thorpe SR, Baynes JW. Protein glycation, mitochondrial dysfunction, and cardiovascular disease. Cardiovascular Diabetology 2019;18(90). Semba RD, Bandinelli S, Sun K, Guralnik JM, Ferrucci L. Plasma carboxymethyl- lysine, an advanced glycation end product, and all-cause and cardiovascular disease mortality in older community-dwelling adults. Journal of the American Geriatrics Society 2010;58(10):1874–1880.",
  "authors": [
    {
      "affiliations": [
        "University of Wolverhampton"
      ],
      "name": "Nazia Aga"
    },
    {
      "affiliations": [
        "University of Wolverhampton"
      ],
      "name": "Paul Kirkham"
    }
  ],
  "title": "P34  Regulation of fructosamine-3-kinase (FN3K) in aortic smooth muscle and endothelial cells: implications for cardiovascular disease",
  "uid": "7887bec8-f751-52a8-a56b-655088198ea0"
}