Effect of fibrates on VLDL and LDL lipoprotein composition and parameters of their oxidation in hypertriglyceridemia
Zeman, M.; Zák, A.; Tvrzická, E.; Konárková, M.; Stípek, S.
Casopis Lekaru Ceskych 141(7): 211-216
2002
ISSN/ISBN: 0008-7335 PMID: 12053756 Document Number: 541350
Meta-analyses of epidemiological studies proved that hypertriacylglycerolemia (HTAG) is an independent CHD risk factor. The VLDL lipoproteins, which are the main TAG carrier, are precursors of atherogenic LDL and their increased concentration is related to the decrease of antiatherogenic HDL, increased ratio of small, dense LDL and represents one of the causes of the endothelial dysfunction. According to some authors, HTAG is one of the factors of the oxidation stress. 45 patients of the studied group received 200 mg of micronized fenofibrate per day for six weeks. Before the beginning and after the end of treatment, following examinations were carried out: concentration of plasma lipids, lipoproteins, and apolipoproteins, composition of fatty acids (FA) in main lipid plasma classes and LDL (phosphatidylcholine--PC, TAG, cholesteryl esters--CE) and lipoperoxidation in VLDL and LDL, isolated by preparative ultracentrifugation. In plasma, the treatment of HTAG led to a significant decrease of TC, TAG and apo-B concentration and to the increase of cholesterol concentration in HDL and in both HDL2 and HDL3 subfractions. In isolated LDL particles we observed a decrease of the TAG portion (by 25%) together with significant lag phase prolongation (by 33%, P < 0.05) and peak time retardation (by 24%, P < 0.05). In VLDL particles the concentration of cholesterol became smaller (by 28%), TAG (by 26%), phospholipids (by 28%) (in all groups P < 0.005) and the lag phase became significantly longer (by 16%, P < 0.01). Treatment with fenofibrate significantly reduced the linoleic acid (18:2n-6) in PC and TAG plasma, CE and TG LDL, in a higher ratio of palmitoleic acid (16:1n-7) in CE LDL, oleic (18:1n-9) in PC LDL, in significant concentration of total monoenic FA in PC and CE LDL and to a significant increase of the concentration of myristic acid (14:0) in CE and myristic and stearic acids (18:0) in TAG LDL. From our results it is possible to conclude that the six-week long treatment of HTAG with micronized phenofibrate led to significant modification of LDL and VLDL composition accompanied by their lower lipoperoxidation indexes. These favourable changes in oxidability were accompanied with changes in the composition of FA in CE, TAG and PC plasma as well as LDL.