Combating atherosclerosis with heavy PUFAs: Deuteron not proton is the first
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 F2a (8-iso-PGF2a) and its b-oxidation metabolite 2,3-dinor-5,6-dihydro-8-iso-PGF2a
was found to be almost 2-fold elevated in coronary heart disease patients compared to healthy age- and gender-matched subjects. A formidable challenge in using 8-iso-PGF2a 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. Reversely, prostaglandin F2a (PGF2a), 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. These ramifications render difficult to estimate to which extent non-enzymatic and enzymatic reactions contribute to biological 8-iso-PGF2a, MDA and other LPO products from PUFAs.