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Statins enhance arachidonic acid synthesis in hypercholesterolemic patients
P Risé1, F Pazzucconi, C R Sirtori
1Department of Pharmacological Sciences, Niguarda Hospital, University of Milan, via Balzaretti 9, 20133 Milano, Italy.
Background And Aim:
It has been shown that statins enhance arachidonic acid biosynthesis from linoleic acid in vitro, and there is also evidence that statin-treated patients have high plasma and cellular arachidonic acid levels. The aim of this study was to investigate the possible effects of statins on the desaturating steps of arachidonic acid biosynthesis in patients.
Methods And Results:
Plasma polyunsaturated fatty acids (percentages and concentrations), total cholesterol, LDL-cholesterol and triglycerides were measured in three groups of hypercholesterolemic patients before and after treatment with statins or fibrates for about three years, or before and after four months on a low-fat diet. As expected, there was a significant reduction in plasma total cholesterol (-23%) and LDL-cholesterol (-27%) levels in the statin group, and a significant reduction in triglycerides (-29%) and some decrease in total cholesterol (-12%) in the fibrate group; no change was observed in the control group. The selective increase in plasma arachidonic acid levels (in terms of absolute concentration and as a percentage of total fatty acids) was of the same order as the reduction in cholesterol, and the selective increase in the product/precursor ratios for delta 5 desaturation in the statin group indicated that this key step in arachidonic acid synthesis is affected.
Conclusions:
Our data show that an increase in arachidonic acid synthesis due to enhanced delta 5 desaturation is a major effect of statin treatment, and has the same order of magnitude as the reduction in plasma cholesterol levels.