Number of glucocorticoid receptors in lymphocytes and their sensitivity to hormone action.

The study demonstrated a decreased level of glucocorticoid receptors (GR) in peripheral blood lymphocytes from hypercholesterolemic subjects, and an elevated level in patients with acute myocardial infarction. In the lymphocytes with a high GR number, dexamethasone inhibited [3H]-thymidine and [3H]-acetate incorporation into DNA and cholesterol, respectively, in the same manner as in the control cells. On the other hand, a decreased GR number resulted in a less efficient dexamethasone inhibition of the incorporation of labeled compounds. These data showed that the sensitivity of lymphocytes to glucocorticoids changed only with a decrease of GR level.

[Reduced cell sensitivity to glucocorticoid hormones in hypercholesterolemia]. / Snizhenie kletochnoi chuvstvitel'nosti k gliukokortikoidnym gormonam pri giperkholesterinemii.

The number of 3H-dexamethasone binding sites in lymphocytes of subjects with hypercholesterolemia (HCS) was found to be decreased as compared to the receptor level in normolipidemic patients (N). In HCS-lymphocytes, the dexamethasone-induced inhibition of 3H-thymidine and 14C-acetate incorporation was less pronounced (by 20% and 22%, respectively) than in control cells, which is suggestive of the decreased sensitivity of HCS-lymphocytes to the hormone. An addition of 5-25% HCS blood sera to human skin fibroblast cultures caused a 10-50% decrease in the number of 3H-dexamethasone binding sites and diminished the Kd values 2-3 times. Lipid-depleted HCS-sera had no effect on the glucocorticoid reception in fibroblasts, whereas very low (VLDL) and low (LDL) density lipoproteins inhibited the 3H-dexamethasone binding to the cells. The most potent inhibiting effect was exerted by VLDL (both N-VLDL and HCS-VLDL). HCS-VLDL were more effective than N-LDL. HCS-HDL and N-HDL did not effect the 3H-dexamethasone binding to fibroblasts. In cells preincubated with VLDL dexamethasone inhibited the incorporation of 3H-thymidine and 14C-acetate less intensively (by 27% and 20%, respectively) than in control fibroblasts. The experimental results are suggestive of a decreased sensitivity of peripheral HCS-cells to glucocorticoids, which may shed some light on the mechanism of hypercholesterolemia realization into coronary heart disease and atherosclerosis.

Reduced sensitivity of peripheral cells to glucocorticoids in hypercholesterolemia.

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.

[Population genealogy research on ischemic heart disease among the population of Alma-Ata]. / Populiatsionno-genealogicheskoe issledovanie ishemicheskoi bolezni serdtsa sredi naseleniia Alma-Aty.

Analysis of the results of a populational genealogical and epidemiological study into coronary heart diseases (CHD) carried out among the nonorganized male population aged 20-54 years living in Alma-Ata supports the importance of hereditary predisposition to the development of CHD as one of the leading risk factors for the illness. The rate of heart attacks (HA) in the diseases histories of the fathers and mothers of CHD persons was higher than among the parents of healthy persons. The mean values of cholesterol and triglyceride levels appeared much more significant in persons having both parents with a history of HA.

[Changes in the fatty acid composition of erythrocyte and platelet membranes after diet therapy in patients with hyperlipoproteinemia type II]. / Izmenenie sostava zhirnykh kislot membran éritrotsitov i trombotsitov pod vliianiem dietoterapii u bol'nykh giperlipoproteidemiei II tipa.

Fatty acid spectrum of blood plasma, erythrocyte, and thrombocyte membranes as well as its alterations after diet therapy, containing polyunsaturated/saturated fatty acids at the ratio of I and less than 350 mg of cholesterol per a day, was studied in patients with hereditary hypercholesterolemia using gas chromatography. Content of linoleic acid was increased and that of oleic and arachidonic acids--decreased in lipids of the patients blood plasma as compared with healthy persons; an increase of linoleic acid was also detected in thrombocyte lipids. Alterations in fatty acid spectrum of erythrocyte membranes were less pronounced. After the course of diet therapy within I month a further increase in content of linoleic acid was observed in blood plasma. Under these conditions efficiency of essential fatty acids incorporation into lipid structures of thrombocyte membranes was higher and of erythrocytes--lower in the patients as compared with healthy persons. Possible alimentary correction of fatty acid spectrum in blood lipids is discussed.

[Plasma levels of testosterone and lipid-protein components of high density lipoproteins and their subclasses in the native population of the Chukotka national autonomic region]. / Soderzhanie testosterona i lipidno-belkovykh komponentov lipoproteidov vysokoi plotnosti i ikh podklassov v plazme krovi korennogo naseleniia Chukotskogo natsional'nogo avtonomnogo okruga.

In a representative aboriginal male Chukchi population, relationships were examined between major lipid-protein components of high-density lipoproteins (HDLP) and their subclasses (HDLP2 and HDLP3) and physiological plasma testosterone patterns. A single-trend correlation was established between cholesterol and phospholipids of each of the HDLP subclasses, and plasma triglycerides and testosterone. Apo-AI for each of the HDLP subclasses showed different trends of correlation with both triglycerides and normal range of testosterone. The findings are indicative of different patterns in the formation of HDLP2 and HDLP3 particles.

[Phospholipid characteristics of the HDLP2 and HDLP3 composition in dysalphalipoproteinemia]. / Osobennosti fosfolipidngoo sostava LPVP2 i LPVP3 pri disal'falipoproteidemii.

There has been determined the phospholipid composition in HDLP2 and HDLP3 obtained from the blood plasma of males with different cholesterol (CS) level of HDLP. An increase in CS of HDLP is shown to be associated with the increase in a percentage of phosphatidylcholine, a proportion of phosphatidylcholine/sphingomyelin and a reduction of the percentage of sphingomyelin (mainly in HDLP2) and to a lesser extent--in HDLP3. A direct correlation has been established between the level of CS of HDLP obtained from the blood plasma of males living in 3 different geographical zones of the USSR and the indices of the phospholipid composition of HDLP2. Changes found in the phospholipid composition of HDLP3 in dysalphalipoproteidemia are associated with a difference in the triglyceride level of the blood plasma.

[Cholesterol of the high-density lipoprotein subclasses in the native inhabitants of the Chukchi National Autonomous Okrug]. / Kholesterin podklassov lioproteidov vysokoi plotnosti u korennykh zhitelei Chukotskogo natsional'nogo avtonomnogo okruga.

The authors studied the content of total cholesterol (Ch), triglycerides (TG), CS of high density lipoprotein (HDL2 and HDL3) subclasses and testosterone in blood plasma of 30-59-year-old males, natives or newcomers of Chukotsk, and compared the results with the corresponding values determined in the male population of Moscow. It was established that the mean HDL Ch concentration in blood plasma was higher and the content of TG and to a lesser degree that of total CS, was lower in the Chukchi males than in the male Moscow population and in the newcomers who were examined. It was also shown that in hypo- and hyper-alphalipoproteinemia in all groups examined, the content of HDL2 Ch changed for the most part (decreased or increased, respectively) while the level of HDL3 Ch remained relatively stable.

[Correlative role of genetic and environmental factors in the cholesterol variability of high-density lipoproteins and their subclasses]. / Issledovanie sootnositel'ni roli geneticheskikh i sredovykh faktorov v izmenchivosti kholesterina lipoproteidov vysokoi plotnosti i ikh podklassov.

The correlative contribution of environmental and genetic factors in determining the levels of cholesterol (CS) of high density lipoproteins (HDLP) and their subfractions (HDLP2 and HDLP3) was studied on a twin model. The predominant role of the genetic component in the interindividual variability of CS HDLP3 both in females and in males and a relatively greater contribution of the environmental component in CS HDLP2 variability were revealed. This explains the greater lability of CS HDLP2 concentrations under different environmental effects.

[Genetic analysis of the structure of connections between certain physiologic traits. I. Analysis of arterial pressure indices]. / Geneticheskii analiz struktury sviazei mezhdu nekotorymi fiziologicheskimi priznakami. Soobshchenie I. Analiz pokazatelei arterial'nogo davleniia.

Genetic analysis of the structure of phenotypical correlatin between systolic and diastolic blood pressure (BP) was carried out on a twin sample (72MT, 122 - of the same sex and 79 - of different sexes DT at the age of 18-40) taken from the Twin Register of the Institute of Medical Genetics, Academy of Medical Sciences of the USSR. Because of heterogeneity of general dispersions of ABP characteristics in different twin subgroups, the method is suggested of a correction of coefficient values of interclass correlation which for the systolic ABP was rMT=0.558, rDT=0.252, and for the foastolic ABP was rMT=0.454, rDT=0.271. Estimations of heritability were 0.612 for systolic and 0.365 for diastolic ABP. There was observed a significant genetic correlation in ABP characteristics which made ra=0.76; the correlation conditioned by general environmental factors being re=0.69. Thus, 76% of genetic and 69 environmental factors, determining the levels of systolic and diastolic ABP were general. The significance was discussed of the obtained results in the light of physiological pharmacological and clinical data.