Enhanced removal of cholesterol from macrophage foam cells to serum from type IV hypertriglyceridemic subjects.

Hypertriglyceridemia being an independent cardiovascular risk factor, we have compared the potential of sera from asymptomatic hypertriglyceridemic (HTG) type IIb, type IV or normolipidemic (NLP) subjects to promote both fractional cholesterol efflux and cellular cholesterol mass changes using macrophage foam cells. The J774 cells loaded with cholesterol by incubation with acetylated LDL were incubated in the absence or presence of cAMP to upregulate ABCA1 (ATP binding cassette transporter A1) and then incubated for 24h with 1% serum. Compared with NLP, type IV sera exhibited a major increase in ABCA1-dependent efflux while type IIb sera exhibited a moderate but not significant increased ABCA1-mediated efflux. Moreover, positive correlations were established between ABCA1-dependent efflux and the serum prebeta-HDL or TG concentrations. The major finding was that the sera from type IV induced higher total cholesterol and cholesteryl ester mass depletions from ABCA1-expressing cells compared with other groups. Moreover, negative correlations were obtained between total cholesterol or cholesteryl ester mass changes and serum prebeta-HDL levels. In conclusion, we demonstrated for the first time that the serum prebeta-HDL present in high proportions in type IV HTG subjects are not only responsible for higher cholesterol efflux potential but also for increased abilities to promote net removal of cholesterol from macrophage foam cells.

[The diversity of the forms of atherosclerosis]. / Pro riznomanitnist' form aterosklerozu.

On the grounds of experimental investigations and study of immunity in patients with atherosclerosis data evident of existence of two types of the disease were obtained. The first type, caused exceptionally by disorders of lipid metabolism, develops in young people. The second, related mainly to lesions of vascular wall due to immune disorders, occurs in the elderly.

[Anti-kappa elastin antibody titer in the sera of patients with hyperlipoproteinemia type II, III and IV]. / Miano przeciwcial przeciwko kappa elastynie w surowicach chorych na hiperlipoproteinemie typu II, III i IV.

Titre of antibodies against elastin degradation product (kappa-elastin) was measured in patients with atherogenic types of hyperlipoproteinemia. The hemagglutination technique was used. A significant decrease in titres of the tested antibodies was found. It was the most prominent in IIa, III and IIb types of hyperlipoproteinemia and rather mild in IV type. The authors attempted to explain causes of antibodies titres decrease in tested patients and relate their results with those of other authors.

Determination of anti-elastin peptide antibodies in normal and arteriosclerotic human sera by ELISA.

We adapted a highly sensitive and reproducible ELISA technique for the determination of anti-elastin peptide antibodies of IgG type AEAb-IgG) and IgM type AEAb-IgM) in human sera. The determination was performed in the sera of 265 normal and diseased persons. The pathologies studied included obliterative arteriosclerosis of the legs, ischemic heart disease, stroke, diabetes mellitus, type IIb and IV hyperlipoproteinemia and hypertension. No clearcut correlation could be found between AEAb and age. In contrast, in arteriosclerotic patients and especially in obliterative arteriosclerosis of the legs and ischemic heart disease, the concentration of AEAb-IgG was significantly increased. The AEAb-IgM showed no change in the studied diseases. Both types of AEAb were decreased in type IV hyperlipoproteinemia. Anti-elastin antibodies may be involved in the pathomechanisms of the above diseases and the determination of antibody concentrations may be of some help in obliterative arteriosclerotic diseases.

Cell-mediated immune response in patients with type IIa, type IIb and type IV primary hyperlipoproteinaemia.

Plasma lipoproteins inhibit immune function. Polymorphonuclear cell (PMN) and monocyte activities, and pokeweed mitogen (PWM)-driven B cell differentiation in patients with type IIa, type IIb and type IV primary hyperlipoproteinaemia were evaluated. Evidence is provided for a selective impairment of these functional capacities in type IIa and type IIb hyperlipoproteinaemic patients, while immune responsiveness is unaffected in type IV primary hyperlipoproteinaemia. The data suggest a specific immune dysfunction in patients with type IIa and type IIb primary hyperlipoproteinaemia.

Hypolipidemic therapy modulates expression of apolipoprotein B epitopes on low density lipoproteins. Studies in mild to moderate hypertriglyceridemic patients.

Low density lipoproteins (LDL) of untreated moderate to severe hypertriglyceridemic patients (HTG-LDL) are smaller in size and are relatively enriched in triglycerides and proteins compared with normal LDL (N-LDL). HTG-LDL also manifest defective binding to the LDL receptors of normal cultured human fibroblasts. These structural and functional defects are reversible by effective hypolipidemic therapy. The aims of the present study were to confirm the reversibility of the structural and functional defects in mild to moderate hypertriglyceridemic patients and also to test the hypothesis that therapy improved the binding of HTG-LDL to cells by modulating epitopes of apolipoprotein B (apoB-100) on the surfaces of LDL particles. Fasting plasma samples were obtained from five mild to moderate hypertriglyceridemic patients before and 3 weeks after bezafibrate therapy when mean triglyceride levels were 436 and 157 mg/dl (P less than 0.01), respectively. LDL particles were isolated by zonal ultracentrifugation, characterized chemically, and assayed for cell association and proteolytic degradation in-up regulated normal human skin fibroblasts. LDL immunoreactivity was tested in solid phase competitive binding radioimmunoassays (RIA) using three monoclonal antiLDL antibodies (Mab). Mab 464B1B3 and Mab 465B6C3 react against epitopes in the COOH-terminal (T2/K4) fragment of apoB-100. Mab D7.1 reacts with an epitope in the midportion (T3/K3) fragment. Mab 464B1B3 inhibits the binding of LDL to the LDL receptor. Hypolipidemic treatment altered the composition of LDL. Mean LDL triglycerides fell from 9.4 to 5.8% of LDL mass (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased level of the complement C3 protein in endogenous hypertriglyceridemia.

When compared to values obtained in normalweight, normolipidemic control subjects, the level of complement C3 protein and total complement activity (CH50) were found to be obviously decreased in patients with decompensated cirrhosis of the liver and slightly but significantly increased in subjects with type IIb and type IV hyperlipoproteinemia. C3 protein level was positively correlated with the concentration of serum cholesterol, the logarithm of serum triglyceride concentration, serum pseudocholinesterase and total complement activity. There were no significant differences concerning C3 protein level between hyperlipidemic subjects with clinical atherosclerosis and those without documented vascular disease. It is suggested that accelerated lipoprotein turnover occurring in many subjects with type IIb and type IV hyperlipoproteinemia might enhance the synthesis of several liver produced plasma enzymes and proteins including the C3 protein of the complement system.

[Immune reactivity in patients with disorders of lipid metabolism]. / Immunreaktivität bei Patienten mit Fettstoffwechselstörungen.

The accidental observation of a selective IgM-deficit in a family with hyperlipoproteinaemia type II caused the working hypothese of close interactions of lipometabolism and immunoreactivity. In 69 patients with hyperlipoproteinaemia the quantitative determination of the immunoglobulins G, A and M was performed by the Mancini-test. All decreased values were repeated in a second determination at another moment. In 9 patients with hyperlipoproteinaemia and deficit of immunoglobulins we determined the T-lymphocytes by means of the sheep erythrocyte rosette test, the B-lymphocytes with the help of the method of direct immunofluorescence and the mouse erythrocyte rosette test. Altogether 14 of the 69 patients with hyperlipoproteinaemia showed reproducible deficit of immunoglobulins, which is statistically significant. The immune defect appeared above all as decrease of IgA (11 patients) isolated 8 patients or in combination with IgM-deficit (2 patients) and IgG-deficit (1 patient). 2 resp. 1 patient showed selective IgG- or IgM-deficit. Clinical symptoms of an immune defect were not recognizable anamnestically and prospectively. In the 9 patients who were immunologically further characterized the T-lymphocytes were in the region of the norm or were increased, the subpopulation of B-lymphocytes which reacted with mouse erythrocytes was normal or increased. The classification to the types of hyperlipoproteinaemia of the altogether 14 deficient patients showed the order IIa, IV, IIb. The original working hypothesis could be supported by the present findings, though an obvious clinical importance is not yet to be recognized. Changes of the membrane lipids of lymphocytes, interventions through the prostaglandin system and effect via suppressor cells must be discussed causally.