dinoprost and Hyperlipidemia--Familial-Combined

Oxidized low-density lipoprotein (Ox-LDL)is implicated in the pathogenesis of atherosclerosis. Circulating oxidation-specific epitopes on plasma Ox-LDL has been linked with coronary artery disease, but its determinants and its association with early development of atherosclerosis in familial combined hyperlipidemia (FCHL) has not been very well studied. This study aimed to investigate the determinants of the circulating Ox-LDL and the association between Ox-LDL and carotid intima-media thickness (IMT) in asymptomatic members of FCHL families.. Ox-LDL, susceptibility of LDL to oxidation in vitro, plasma 8-isoprostane and antioxidants, lipids and lipoproteins, LDL particle size, and carotid IMT were measured in 150 asymptomatic FCHL family members. Affected FCHL family members had reduced LDL particle size and lag time for LDL oxidation, increased plasma levels of Ox-LDL, increased plasma urate and alpha-tocopherol, and a trend for the increase of 8-isoprostane as compared with nonaffected FCHL. Ox-LDL was independently associated with serum LDL cholesterol, apoB, and 8-isoprostane in multivariate analysis but only univariately correlated with LDL particle size and lag time for LDL oxidation. In addition, Ox-LDL was significantly associated with carotid mean IMT independently of other clinical and biochemical variables in a multivariate model.. Serum LDL cholesterol, apoB levels, and 8-isoprostane were the most important determinants of Ox-LDL. Ox-LDL is independently associated with carotid IMT in asymptomatic FCHL family members and can be used as a marker of early atherosclerosis in FCHL.

Topics: Adult; Antioxidants; Biomarkers; Carotid Arteries; Carotid Artery Diseases; Dinoprost; Disease Susceptibility; Female; Finland; Humans; Hyperlipidemia, Familial Combined; Lipids; Lipoproteins; Lipoproteins, LDL; Male; Particle Size; Tunica Intima; Tunica Media; Ultrasonography

Low-density lipoproteins (LDL)-apheresis is a well established treatment of severe hypercholesterolemia resulting in fast clinical improvement and angiographically proven regression after 6 months of therapy. The underlying mechanisms, beside lipoprotein removal, are still under debate. Recently, oxidized LDL were shown to be of key importance in foam cell formation and atherosclerotic lesion development. We examined the influence of dextran-sulfate LDL-apheresis on the susceptibility of LDL to oxidation in 6 patients (5 males, 1 female, age: 41-60 years) suffering from severe heterozygous hypercholesterolemia or combined hyperlipidemia. LDL-apheresis influenced the oxidizability of LDL by a significant (P < 0.01) prolongation of the median of lag time (min) for LDL samples (before treatment 75, range: 31-176 versus after treatment 129.5, range 45-286). A significant (P < 0.01) difference could be also observed in the amount of conjugated dienes as expressed by the maximum rate in absorbance (before treatment 15.39, range: 5.29-21.22 versus after treatment 20.20, range 12.88-72.33). Thiobarbituric acid reactive substances (TBARS) formation was significantly decreased in LDL obtained after apheresis treatment as compared to pretreatment LDL. Electrophoretic mobility (EM) of LDL obtained before and after LDL-apheresis revealed a significant increase (P < 0.05) from a mean of 8.8 +/- 0.5 to a mean of 10.5 +/- 0.5 mm. The titers of plasma autoantibodies against oxLDL (oLAb) which varied considerably interindividually, were not influenced by LDL-apheresis treatment. Levels of F2-isoprostanes, as measured by plasma levels of 8-iso-prostaglandin-F2 alpha (8-iso-PGF2 alpha), reflecting oxidative stress, did not change, either. In summary, our findings provide evidence that even one single dextran sulfate LDL-apheresis treatment decreases LDL-oxidizability, which is an additional beneficial effect to that of lipid lowering.

Topics: Adult; Autoantibodies; Blood Component Removal; Dextran Sulfate; Dinoprost; Electrophoresis, Agar Gel; F2-Isoprostanes; Female; Heparin; Humans; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type II; In Vitro Techniques; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Thiobarbituric Acid Reactive Substances

In continuation of investigations on primary hyperlipidaemias, we determined serum thromboxane (TX) B2 and prostaglandin (PG) F2 alpha after standardized blood clotting in patients without hyperlipidaemia and without (group 1, n = 11) or with coronary heart disease (CHD; group 2, n = 5), in patients with familial combined hyperlipoproteinaemia and without (group 3, n = 4) or with CHD (group 4, n = 5), as well as in patients with familial hypercholesterolaemia and CHD (group 5, n = 5). TXB2 was detected by gas chromatography and PGF2 alpha by means of radioimmunoassay. The TXB2 level did not differ significantly between the groups, but there was a tendency to higher values in hyperlipidaemia, while in group 5 the level tended to decrease with rising serum LDL-cholesterol and in group 3 it tended to increase with rising serum apolipoprotein B. The PGF2 alpha level was significantly lower in group 4 than in groups 1 and 3. It showed in group 5 a negative correlation with serum LDL-cholesterol and in group 3 a positive correlation with serum triglycerides.

Topics: Adult; Aged; Apolipoproteins A; Apolipoproteins B; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Dinoprost; Female; Humans; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type II; Lipids; Male; Middle Aged; Thromboxane B2; Triglycerides