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Combating atherosclerosis with heavy PUFAs: Deuteron not proton is the first

  • Dimitrios Tsikas
    Correspondence
    Centre of Pharmacology and Toxicology, Core Unit Proteomics, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
    Affiliations
    Centre of Pharmacology and Toxicology, Core Unit Proteomics, Hannover Medical School, Hannover, Germany
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      Atherosclerosis, diabetes mellitus, hypertension, obesity, and cigarette smoking are established risk factors for cardiovascular disease. In such conditions, elevated concentrations of lipid peroxidation products are found in plasma and urine, suggesting that oxidative stress with its multiple facets, most notably lipid peroxidation (LPO), is a major contributor to the development of atherosclerosis. As an example, creatinine corrected urinary excretion of the F2-isoprostane (F2-IsoP) 8-iso-prostaglandin F (8-iso-PGF) and its β-oxidation metabolite 2,3-dinor-5,6-dihydro-8-iso-PGF was found to be almost 2-fold elevated in coronary heart disease patients compared to healthy age- and gender-matched subjects [
      • Schwedhelm E.
      • Bartling A.
      • Lenzen H.
      • Tsikas D.
      • Maas R.
      • Brümmer J.
      • Gutzki F.M.
      • Berger J.
      • Frölich J.C.
      • Böger R.H.
      Urinary 8-iso-prostaglandin F2alpha as a risk marker in patients with coronary heart disease: a matched case-control study.
      ]. A formidable challenge in using 8-iso-PGF and other LPO products such as malondialdehyde (MDA) as markers of lipid peroxidation is their enzymatic production from arachidonic acid and other polyunsaturated fatty acids (PUFAs) by cyclooxygenase (COX) in platelets and other types of cells [
      • Tsikas D.
      Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: analytical and biological challenges.
      ,
      • Tsikas D.
      The dilemma of oxidative stress personified by the diprosopus 8-iso-prostaglandin F and prostaglandin F.
      ]. Reversely, prostaglandin F (PGF), which has been believed for decades to be exclusively formed by the COX-catalyzed oxidation of arachidonic acid, is now considered to be formed non-enzymatically as well [
      • Tsikas D.
      Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: analytical and biological challenges.
      ,
      • Tsikas D.
      The dilemma of oxidative stress personified by the diprosopus 8-iso-prostaglandin F and prostaglandin F.
      ]. These ramifications render difficult to estimate to which extent non-enzymatic and enzymatic reactions contribute to biological 8-iso-PGF, MDA and other LPO products from PUFAs.

      Keywords

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