[Prospective trends in studies on the role of lipoproteins in human atherogenesis: their effect on disease progression, diagnostic value and the possibility of corrective interventions].
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Biomedical subjects
Publications and source records attributed to N V Perova.
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It has been found that lymphocytes of hypercholesterolemic (HCh) subjects are characterized by a reduced number of glucocorticoid receptors (GcR) as compared with the cells of normolipidemics (N). Addition of HCh-sera or very low density lipoproteins, or low density lipoproteins isolated both from HCh-sera and N-sera to cultured human skin fibroblasts brought about a fall in the number of GcR in the cells. High density lipoproteins had no effect on GcR level. Dexamethasone was less effective in inhibiting cholesterol synthesis from [14C]acetate in the lymphocytes and fibroblasts with a reduced number of GcR. In the presence of dexamethasone (I x 10(-8)M) in fibroblast growth medium, reduced number of GcR (due to preincubation with very low density lipoproteins) led to a substantial increase in cholesterol synthesis. These findings indicate that the sensitivity of peripheral cells to glucocorticoids is decreased in HCh which might be one of the trigger mechanisms of atherogenesis.
Random representative samples of 20- to 54-year-old men and 11- and 14-year-old boys were investigated in different regions of the country in order to elucidate the pattern of the formation of major coronary risk factors. The prevalence of coronary heart disease was found to vary widely in 20- to 54-year-old males and show correlation to risk factor levels in most centres. Difference in the incidence of hyperdiglyceridemia and smoking can already be seen in 11-year-old boys, and variation in hypercholesterolemia and excessive body weight, after 14 years of age.
Gradient gel electrophoresis was used to study the changes in the HDL subfractional spectrum according to the particle size during their interaction with hepatoma Hep-G2 cells and human skin fibroblasts. Incubation of normolipidemic sera with Ch-loaded fibroblasts resulted in a drop in small particle (HDL3a' HDL3b, HDL3c) and, a rise in large particle (HDL2b, HDL2a) proportions. In contrast, incubation of the same sera with hepatoma cells caused a decrease in HDL2b proportion and a HDL3a release. Incubation of hypoalphacholesterolemic sera with fibroblasts showed a decrease in HDL3b, HDL3c particles and an increase only in HDL2a. The proportion of HDL2b rose considerably when the sera were incubated with hepatoma cells. It is concluded that not only low HDL sera levels, but also the formation of defective HDL2b particles which interact less effectively with liver cells, are characteristic of hypoalphacholesterolemia.
The level of blood plasma apolipoproteins A-I and B was studied in Moscow and Prague residents with different types of hyperlipoproteinaemia (HLP). The analysis proceeded in two directions. On the one hand, lipoprotein (LP) spectra in residents of both cities with the same type of LP disturbance (HLP type IIa, IIb or IV) were compared; in Prague lipid and apolipoprotein content was compared in inhabitants with a normal lipid level and those with HLP types I, III and V. The analysis showed that inhabitants of Prague with types II and IV HLP have a higher concentrations of high density LP cholesterol. At the same time, it was found that the apolipoprotein profile of blood plasma LP in HLP patients was similar to that in patients living elsewhere. The authors regard comparative study of LP system disturbances in residents of different cities and countries differing in their geographical, ethnic and ecological conditions as a promising approach to understanding the mechanisms responsible for the development of HLP.
The authors compare the prevalence of risk factors of atherosclerosis and ischaemic heart disease (dyslipoproteinaemia, elevated arterial pressure, overweight, smoking, low physical activity) in representative samples of 11- and 14-year old school-children in Moscow, Novosibirsk and Tallin. The number of pupils subjected to medical examination totalled 3369; the respondence rate was 87-92%. There appeared a number of regional differences: the study in Moscow showed the highest prevalence of elevated arterial pressure and overweight, in Novosibirsk - hypertriglyceridaemia, in Tallin - hypercholesterolaemia. The most unfavourable situation was registered in school-children in Novosibirks. The authors conclude that when planning preventive measures among the population it is necessary to take into account regional specificities and differences in the intensity of risk factors in children populations.
A representative random sample of 3,308 male residents aged 20-59 years from a Moscow district was examined. Only 74% of them participated in the study. Routine epidemiological methods were used to identify various forms of coronary heart disease (CHD). The prevalence of CHD was 9.7% in the population with the incidence of definite CHD of 5% and possible CHD of 4.6%. The prevalence of CHD was significantly associated with age, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, hypoalphacholesterolemia, and obesity. The findings should be borne in mind while planning preventive measures in the population of working age.
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Total cholesterol, triglycerides, high and low density lipoprotein cholesterol were measured in 40- to 59-year-old males from Moscow, Tallinn, a mountain village in the Caucasus and settlements in the Chukotka. Mean values, and 10th and 90th percentiles were determined for each of the populations examined. The Moscow and Tallinn populations were found to be similar biochemically and differ from rural populations. Dyslipoproteinemias were more atherogenic in urban residents, as compared to their rural counterparts. It is suggested that dyslipoproteinemias have geographic and ethnic determinants that may contribute to the degree of atherogeny implicit in any type of lipid metabolic disorders.
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Heterogeneity of lipoprotein particles of the main classes is shown in primary and secondary hyperlipidemias. It displays biochemical, physical and chemical impairments in the system of lipid transport. Aggregation is one of lipoprotein heterogeneity manifestation. Morphological electron microscopic characteristic is one of the main methods in lipoprotein abnormal heterogeneity diagnosis.
A comparison is made of two epidemiological studies conducted within an eight-year interval on randomly selected independent samples of male population aged 40-59 years in one of the municipal districts of Moscow. In the years 1975-1977, 3908 men (response rate 77.7%) were examined, in 1983-1984 1662 men (response rate 72.0%). The comparison concentrated on the detection of changes in the incidence of major risk factors of IHD: arterial hypertension, dyslipoproteinaemia, overweight, smoking. Over the period under review, the incidence of hypertension and overweight did not practically change, a statistically significant decrease occurred in the incidence of hypercholesterolaemia and hyperglyceridaemia; the incidence of hypo-alpha-cholesterolaemia did not change. A significant drop (by 10.2%) occurred in cigarette smoking.
The paper is devoted to the characterization of the spectrum of lipoproteins (LP) including the determination of the content of apoproteins AI and B by quantitative "rocket" immunoelectrophoresis in 75 male patients aged 40 to 59 with normal body mass, with types I and II diabetes mellitus, in the state of compensation of carbohydrate metabolism, with and without signs of coronary heart disease. Sixty healthy men were controls. It was shown that in diabetic (types I and II) patients with CHD changes in LP spectrum values were similar to those in CHD patients without diabetes. In patients with type I diabetes without clinical signs of CHD, LP spectrum values including the content of apo-AI, apo-B and the ratio of apoB/apo-AI did not differ from those of the controls. Changes in LP-containing apo-AI expressed not only in the reduction of the total content of CH-HDIP but also in change of the composition of HDLP particles, were found in diabetic (type II) patients without clinical signs of CHD.
The authors presented the results of a study of the level of blood plasma apo-B and apo-A-I in random samples (by age decades from 20 to 60) of the organized male population (n = 309) and additionally of CHD patients who were not entered into the random samples (n = 82). Age differences in the level of blood plasma apo-B and apo-A-I were noted; a significant positive correlation with age of the level of apolipoprotein B at the age of 20 to 59 and a negative correlation of apo-A-I in males aged 20 to 39 were revealed. By the percentile distribution of apo-LP-B and A-I the relative borders of their high and low values were defined in random samples of males aged 20 to 39 and 40 to 59. Significant differences in the prevalence of high and low levels of apo-B and apo-A-I were demonstrated among patients with CHD and persons without this pathology.
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Total cholesterol, triglycerides and high- and low-density lipoprotein cholesterol were measured in a study of 40-59-years-old male populations in Moscow and Kharkov. Hypercholesterolemic individuals were identified, using standard criteria, in both cities. Although mean lipid parameters were similar in individuals with second-type hyperlipoproteinemia from Moscow and Kharkov, the pattern of hypercholesterolemia was different in terms of the lipoprotein spectrum. It is concluded that detailed differentiation of second-type hyperlipoproteinemia is essential for the identification of major mechanisms of the atherogenic potential of hypercholesterolemia in different populations.
The sera from 62 of 68 patients with coronary heart disease (CHD) caused a two to five fold elevation in the intracellular cholesterol in primary cultures of subendothelial cells derived from grossly normal intima of human aorta. The sera from 33 of 42 healthy subjects did not show atherogenic properties in culture. Atherogenic potential correlated directly with the serum apolipoprotein-B-apolipoprotein A1 ratio, but not with the level of total cholesterol, high-density-lipoprotein cholesterol, apo-B, or apo-A1. The sera from patients with CHD also facilitated deposition of lipids in the medial smooth muscle cells of human aorta and mononuclear blood cells, though to a lesser degree. They had no such effect on endothelial cells of human aorta and umbilical vein, or human embryo fibroblasts.