[The application of lipoprint-system for analysis of sub-fractional spectrum of lipoproteins of blood serum.]

The lipoproteins of low and high density are presented by heterogeneous specter of particles differing by size, density, charge, composition and functional characteristics. The prevalence of small dense particles of lipoproteins of low and high density in blood plasma is associated with higher risk of development of coronary heart disease. The identification of subfractional spectrum of lipoproteins in clinical purposes is complicated because of requirement of expensive equipment and reagents and extended time of implementation. The lipoprint-system (Quantimetrix Lipoprint LDL/HDL System, USA) based on the vertical electrophoresis using 3% polyacrilamid gel, permits shortening time of sub-fractioning of lipoproteins up to three hours. In the spectrum of apoB-containing lipoproteins of very low density, intermediate density, C, B, A, lipoproteins of low density 1 and 2, small dense (lipoproteins of low density 3-7) are singled out. In the spectrum of lipoproteins of high density up to 10 sub-fractions associated in three groups and represented by large (lipoproteins of high density 1-3), intermediate (lipoproteins of high density 4-7) and small (lipoproteins of high density 8-10) particles are singled out. The article describes technique of identification of spectrum of particles of lipoproteins of low and high density in human blood serum. The conditions of implementation of experiments are presented. The advantages and limitations of technique are indicated. The number of examples of application of indices of sub-fractional spectrum of lipoproteins as additional markers of evaluation of aterogenity of lipid profile are presented. The conclusion is made concerning possibility of application of technique in clinical laboratory diagnostic.

[Age-related Changes of Left Ventricular Diastolic Function, NT-proBNP Level and Their Association With Leukocyte Telomere Length].

UNLABELLED: With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing of the heart is cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the diastolic function of LV and level of NT-proBNP in people of different ages free of cardiovascular diseases and to assess their relationship with LTL. Our data showed that old age is associated with diastolic dysfunction and increase in the levels of NT-proBNP. The group of older subjects had lower values of E/A (0.96 ± 0.036 vs 1.27 ± 0.03, p < 0.001), Em/Am (0.9 ± 0.035 vs 1.5 ± 0.066) and higher values of IVRT (81 ± 1.56 vs 70 ± 1.23 MS, p < 0.001), DT (198 ± 3.98 vs 175 ± 2.82 MS, p < 0.001), that reflected impairment of LV relaxation. NT-proBNP level was higher in the elderly (100.82 ± 7.1 vs 48.47 ± 6.7 ωg/ml, p < 0.01), but it did not correlate with LTL. The most sensitive to the age parameters of LV diastolic function (E/A and Em/Am ratio) were positively and independently of age associated with LTL (p < 0.001). Older individuals with shorter LTL had significantly lower values of E/A ratio. CONCLUSION: Telomere length appears to be a biomarker of myocardium ageing.

[Age-related Changes of Left Ventricular Diastolic Function, NT-proBNP Level and Their Association with Leukocyte Telomere Length].

With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing of the heart is cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the diastolic function of LV and level of NT-proBNP in people of different ages free of cardiovascular diseases and to assess their relationship with LTL. Our data showed that old age is associated with diastolic dysfunction and increase in the levels of NT-proBNP. The group of older subjects had lower values of E/A (0.96+/-0.036 vs 1.27+/-0.03, p<0.001), Em/Am (0.9+/-0.035 vs 1.5+/-0.066) and higher values of IVRT (81+/-1.56 vs 70+/-1.23 s, p<0.001), DT (198+/-3.98 vs 175+/-2.82 s, p<0.001), that reflected impairment of LV relaxation. NT-proBNP level was higher in the elderly (100.82+/-7.1 vs 48.47+/-6.7 g/ml, p<0.01), but it did not correlate with LTL. The most sensitive to the age parameters of LV diastolic function (E/A and Em/Am ratio) were positively and independently of age associated with LTL (p<0.001). Older individuals with shorter LTL had significantly lower values of E/A ratio. CONCLUSION: Telomere length appears to be a biomarker of myocardium ageing.

[Clinical value of insulin resistance in fasting normoglycemia].

Aim of the study was to clarify the question of the presence of manifestations of insulin resistance (IR) in fasting normoglycemia and to assess their association with risk of development and presence of clinically overt cardiovascular diseases (CVD) caused by atherosclerosis. We included into this study 1127 men and women older than 55 years with normal blood serum level of glucose in fasting state (<6.1 mmol/l) without diabetes mellitus selected from a random sample of Moscow inhabitants (n=1186). In participants selected for this study we determined risk factors, calculated indexes of IR (HOMA-IR) and functional capacity of pancreatic -cells (HOMA-%B) using fasting levels of glucose and insulin. The examined subsample was divided into quartiles according to values of HOMA-IR. It was shown that in the 4-th quartile HOMA-%B was substantially higher than in other quartiles. With this values of body mass index and waist circumference were also highest in the 4-th quartile. Fasting insulin level compared with glucose level contributed more to determination of values of indexes of both IR and functional capacity of pancreatic -cells. In the upper 4-th quartile signs of atherogenic dyslipidemia appearing as higher concentration of triglycerides and lowered concentration of high density lipoprotein cholesterol manifested to the greatest degree. At statistical analysis of probability of CVD with clinical manifestations it was shown that in the 4-th quartile of distribution of HOMA-IR (>2.7) values of odds ratio (OR) of development of arterial hypertension (AH), total CVD, angina pectoris, history of brain stroke were elevated. With that in the 3-rd quartile of distribution i.e. at HOMA-IR >1.9 there were higher ORs of development of AH, CVD, angina pectoris. Thus even in the range of normal fasting glucose concentrations in subjects older than 55 years we detected IR associated with elevated risk of development of atherosclerosis related CVD. For detection of IR it is appropriate to measure in blood serum not only concentration of glucose but also fasting insulin level with subsequent calculation of HOMA-IR and HOMA-%B indexes.

[Metabolic peculiarities of dyslipoproteinemias unrelated to high level of blood cholesterol].

The aim of this study was to reveal whether atherogenic or nonatherogenic properties of dyslipoproteinemias (DLP) not related to high level of blood total cholesterol (C) and low density lipoprotein C (LDL C) are determined only by shifts in serum triglycerides (TG) and/or high density lipoprotein cholesterol (HDL C) levels, or by other lipoprotein system alterations, if any. Biochemical factors regulating both lipid and carbohydrate metabolism were analyzed in two subsamples of Moscow residents aged 55 years with DLP: "high TG and low HDL C" and "normal TG and high HDL C" in comparison with randomly selected subsample assumed as "normal". Specific biochemical indexes of atherogenicity of DLP "high TG and low HDL C" were found, namely: increased apo B/AI ratio; disturbed functional activity of HDL in promoting reverse cholesterol transport expressed as elevated apo AII/AI ratio, decreased apo AI and phospholipids (PL) levels, decreased ratios of C/apo AI and C/PL in HDL, and decreased cholesterol-accepting capacity of HDL. Moreover, while fasting glucose level in subjects from this group remained unchanged, their fasting insulin level and HOMA-IR index were increased. Thus, DLP "high TG and low HDL C" is characterized by some specific metabolic features underlying its involvement into pathogenesis of atherosclerosis and type 2 diabetes mellitus. On the other hand, differences in biochemical parameters of antiatherogenic DLP "normal TG and high HDL C" from random subsample appeared to be opposite to differences from random subsample found for DLP "high TG and low HDL C", being in line with the present concept about their role in determining the antiatherogenicity of this kind of DLP.

Parameters of high-density lipoproteins in patients with arterial hypertension in combination with other components of metabolic syndrome.

Parameters of HDL (concentrations of cholesterol, apoprotein A1, and phospholipids and phospholipid composition) determining their functional properties were studied in patients with arterial hypertension in combination with other components of metabolic syndrome (abdominal obesity, hyperlipidemia, and impaired glucose tolerance). Patients with isolated arterial hypertension did not differ from the control group by the concentration of apoprotein A1 and HDL cholesterol, but had lower content of HDL phospholipids and changed phospholipid composition: lower ratio of phosphatidylcholine and higher relative contents of lysophosphatidylcholine, sphingomyelin, and phosphatidylethanolamine. Parameters of HDL in patients with arterial hypertension associated with other components of metabolic syndrome did not differ from those in patients with isolated arterial hypertension. The observed changes in HDL in patients with arterial hypertension alone or in combination with other components of metabolic syndrome can impair functional capacity of HDL in reverse cholesterol transport, which increases the risk of atherosclerosis.

Association of serum apolipoprotein A-II concentration with combined hyperlipidemia and impaired glucose tolerance.

We studied the relationship of serum apolipoprotein A-II concentration with biochemical parameters of lipid and carbohydrate metabolism, type of hyperlipidemia, and insulin sensitivity in male patients with hyperlipidemia. High concentration of apolipoprotein A-II was associated with increased indices of atherogenic lipoproteins and high-density lipoprotein-mediated reverse cholesterol transport, combined hyperlipidemia, and decreased insulin sensitivity calculated with consideration for glucose and insulin levels in glucose tolerance test and body weight.

[Signs of metabolic syndrome in combinations of hypertension with coronary risk factors].

Anthropometric data, parameters of lipoprotein spectrum and carbohydrate metabolism were obtained from 115 men aged 34-67 years with hypertension. Hypertension combined with any other criterion of metabolic syndrome was associated with deviations of parameters of insulin resistance, blood pressure, body mass index, waist circumference, levels of cholesterol, low density lipoproteins and lipoprotein (a) similar to those observed in complete metabolic syndrome. Combinations of hypertension with hypercholesterolemia and/or excessive body mass were not associated with signs of insulin resistance in the presence of higher then in isolated hypertension values of body mass index, cholesterol, low density lipoprotein cholesterol.

Simvastatin and preparation of polyunsaturated phospholipids produce similar changes in the phospholipid composition of high-density lipoproteins during hypercholesterolemia.

We studied the phospholipid composition of high-density lipoproteins in patients with coronary heart disease and hypercholesterolemia treated with simvastatin (Zocor, inhibitor of the key enzyme of cholesterol synthesis) and preparation of polyunsaturated phospholipids (lipostabil forte). Simvastatin produced a hypolipidemic effect and modulates the phospholipid composition of high-density lipoproteins (similarly to lipostabil forte). These changes contribute to functional activity of high-density lipoproteins in the reverse cholesterol transport.

Impaired antiatherogenic function of high-density lipoproteins in the presence of various risk factors for coronary heart disease.

We studied acception of cholesterol from Fu5AH hepatoma cells by blood serum from subjects with normal level of high-density lipoprotein cholesterol and hyperlipidemia (alone or in combination with other risk factors for coronary heart disease). Cholesterol-binding activity of high-density lipoproteins decreased in subjects with hyperlipidemia alone or in combination with excess body weight and/or arterial hypertension. Impairment of high-density lipoprotein activity was associated with changes in their phospholipid composition.

[Lowering of antiatherogenic significance of high density lipoproteins in obese persons]. / Snizhenie antiaterogennoi znachimosti lipoproteidov vysokoi plotnosti u lits s ozhireniem.

Protein and lipid components of blood serum high density lipoproteins (HDL) responsible for their functional activity were studied before and after fat load in subjects with normal body mass and various types of obesity. Subjects with abdominal obesity compared with those with gluteo-femoral obesity and normal body mass initially had pronounced disturbances in components of HDL and their acceptor capacity. Fat load caused changes of HDL composition in all study groups. Postprandial effect in persons with normal body mass became obvious 6 hours after load while in those with excess mass it occurred earlier - 3 hours after fatty meal. In subjects with gluteo-femoral obesity this effect remained on the same level while in those with abdominal obesity it became more pronounced by hour 6. Contrary to subjects with normal body mass and gluteo-femoral obesity fat load induced changes of HDL components in persons with abdominal obesity were not associated with augmented acceptor capacity of HDL what could be considered as proatherogenic effect.

Effects of simvastatin on the phospholipid composition of high-density lipoproteins in patients with hypercholesterolemia.

We studied the phospholipid composition of high-density lipoproteins in patients with hypercholesterolemia before and after treatment with simvastatin. Individual phospholipids were separated by thin-layer chromatography on glass plates coated with silica gel. It was found that apart from hypolipidemic effect, simvastatin changed the concentration and phospholipid composition of high-density lipoproteins, which improved their cholesterol-accepting and cholesterol-transporting properties.

[High density lipoprotein composition in moscovites with low and high HDL cholesterol level]. / Osobennosti sostava lipoproteidov vysokoi plotnosti pri snizhennom i povyshennom soderzhanii v nikh kholesterina u moskvichei.

AIM: To elucidate if there are any peculiarities in HDL composition in Muscovites with different HDL C levels, and to reveal which HDL components could determine the disturbances in their antiatherogenic properties at higher HDL C level. MATERIAL AND METHODS: Sixty men aged 40-59 years with low HDL C level < 40 mg/dl (36 +/- 0.8 mg/dl; n = 30) and high HDL C level > 50 mg/dl(58 +/- 1.6 mg/dl; n = 30) were compared. Enzymatic, immunonephelometric methods and thin-layer chromatography were used. RESULTS: Men with high HDL C level had higher concentration of apo AI, HDL phospholipids (PL), ratios of HDL C/apo AI and HDL C/HDL PL but lower ratio of HDL C free/HDL PL. The analysis of HDL PL composition revealed in subjects with high HDL C higher proportion of phosphatidylcholine (PC) and lower lysoPC, whereas the relative content of sphingomyelin and phosphatidylethanolamine did not differ between the groups. CONCLUSION: The peculiarities in components of HDL found among men with different HDL C levels could explain less effective HDL atheroprotective properties in Muscovites with elevated HDL C.

Phospholipid composition of high-density lipoproteins reflects lipolysis of triglyceride-rich lipoproteins during hyperlipidemia.

We studied phospholipid composition of high-density lipoproteins in patients with normo- and hypertriglyceridemia treated with various hypolipidemic preparations (simvastatin and fenofibrate). Both preparations changed phospholipid composition of high-density lipoproteins and improved their functional activity. The differences in the phospholipid composition of high-density lipoproteins were probably related to lipolysis of triglyceride-rich lipoproteins catalyzed by lipoprotein lipase and, in particular, hepatic lipase.

[C-reactive protein and defect in lipid transport blood system in patients with rheumatoid arthritis]. / S-reaktivnyi belok i narusheniia lipid-transportnoi sistemy krovi u bol'nykh revmatoidnym artritom.

In 88 patients with rheumatoid arthritis lipid-protein spectrum of the blood serum were determined biochemically and by means of nefelometric technique, C-reactive protein (CRP) was measured with enzyme immunoassay. An increase in CRP concentration was associated with lowering of apoA1 and HDL FL, triglycerides. Thus, elevation of CRP in RA reflects not only activity of inflammation but also defects in serum lipid-transport system by the atherogenic type.

Effects of alcohol on the major steps of reverse cholesterol transport.

The effects of moderate alcohol consumption on the capacity of blood sera to promote acceptance of cholesterol (C) from Fu5AH hepatoma cells, esterification of delivered free C, and transfer of produced cholesteryl esters to apolipoprotein (apo) B-containing lipoproteins have been studied. Twenty male subjects with relatively high (>50 mg/dl, n = 10) and low (<50 mg/dl, n = 10) high density lipoprotein (HDL) C levels consumed for eight weeks red grape wine (0.3 g ethanol/kg body mass per day). Alcohol consumption reduced total C and low density lipoprotein C levels in both groups of subjects. Low HDL C subjects showed an increase in HDL C, apo AI, apo AII, and lipoprotein (Lp) AI particle levels after alcohol consumption. Alcohol did not affect free C efflux from the cells. However, after the following period of substitution of alcohol with an isocaloric amount of red grape juice, cellular C efflux markedly reduced. While lecithin:cholesterol acyltransferase (LCAT) activity increased during alcohol consumption only in subjects with low HDL C, high HDL C subjects showed a significant decrease in cholesteryl ester transfer protein (CETP) activity. At the same time, alcohol consumption reduced the endogenous C esterification rate and increased the transfer of endogenous cholesteryl esters to apo B-containing lipoproteins in both groups. Thus, alcohol consumption in moderate doses enhanced the anti-atherogenicity of the serum lipoprotein spectrum, supporting more effective C efflux from peripheral cells and transport of accepted C to apo B-containing lipoproteins. The effects of alcohol on the reverse cholesterol transport depend on the initial HDL C level.

[High-density lipoproteins in cholesterosis of the gall bladder]. / Lipoproteidy vysokoi plotnosti pri kholesteroze zhelchnogo puzyria.

The composition of serum high-density lipoproteins (HDL) was studied in 64 patients with polypous cholesterosis (PC). The spectrum of serum lipids in patients with PC was characterized by the lower concentrations of HDL cholesterol (42.0 +/- 2.5 mg/dl; p < 0.05) and higher concentrations of low-density lipoproteins (LDL) cholesterol (169.9 +/- 6.9 mg/dl; p < 0.01) than those in the controls. The decreased HDL cholesterol, or hypoalphacholesterolemia was associated with quantitative changes in HDL phospholipids (PL) (66.48 +/- 3.4; p < 0.01) and with changes in the composition of individual PL by lowering the proportion of lecithin (47.13 +/- 2.19 mg/dl; p < 0.01). It may be suggested that the lower amount of HDL cholesterol is caused by the decreased HDL acception of free cholesterol from the peripheral cell membranes due to the impaired complexation of PL with free cholesterol and associated the altered PL composition of the superficial monolayer of a lipoprotein particle. At the same time the physicochemical changes in Hdl superficial layer are a cause of abnormal free cholesterol esterification and the impaired plunge of esterified cholesterol into the nucleus of a HDL particle, which facilitates the conversion of HDL to LDL and may explain elevated LDL levels in cholesterosis. The findings suggest that serum lipids are involved in the development of cholesterosis.

Cerivastatin modulates antiatherogenic properties of high-density lipoproteins in patients with coronary heart disease and hyperlipidemia.

The effects of cerivastatin on antiatherogenic properties of high-density lipoproteins were studied in patients with coronary heart disease and hyperlipidemia. Apart from hypolipidemic effects, cerivastatin changed the phospholipid composition of high-density lipoproteins and improved their cholesterol-acceptor properties. This effect was most pronounced in the serum from patients with low content of high-density lipoprotein cholesterol. These data indicate that cerivastatin modulates antiatherogenic properties of high-density lipoproteins.

[The lipid-protein indices of the blood cholesterol transport system in systemic lupus erythematosus]. / Lipidno-belkovye pokazateli sistemy transporta kholesterina krovi pri sistemnoi krasnoi volchanke.

AIM: To assess parameters of blood cholesterol lipid-protein spectrum and characteristics of blood cholesterol (C) transport system in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Lipid-protein blood spectrum was studied in 60 patients (45 females and 15 males) with verified SLE aged 15-44 years (mean age 28.9 +/- 8.1 years). The duration of the disease varied from 2 months to 28 years (mean 8.6 +/- 6.6 years). SLE course and activity were defined according to V. A. Nasonova's classification. The control patients (35 healthy subjects) were matched by age (30.0 +/- 6.1 years) and gender (27 females and 8 males). RESULTS: Elevated levels of C and C of low-density lipoproteins (LDLP), triglycerides (TG) were found in 35% and 30% of patients, respectively. C of high-density lipoproteins (HDLP) was low in 32% of patients. HDLP phospholipids were also subnormal, their proportion changed: concentrations of phosphatidylcholine were low, those of lisophosphatidylcholine, sphingomyelin, diethanolamine, cardiolipin were higher than in the controls. TG and proportion apo/B/AI were higher, content of HDLP components low in patients with the disease duration up to 5 years. Patients with highly and moderately active SLE had high levels of TG, apo/B, apo/B/apo/AI, low levels of HDLP C, apo/AI and HDLP phospholipids. CONCLUSION: Marked dyslipidemias were detected in 1/3 of SLE patients. Cholesterol transport changes arise at early SLE stages. Alterations in the blood lipid-protein spectrum appeared more pronounced and atherogenic in maximal SLE activity. Quantitative and qualitative shifts in HDLP composition induce changes in antiatherogenic properties of relevant lipoproteins in SLE patients.