Lipid profile and the deformability of the erythrocytes in athletes

Correlations between rheological properties of blood (viscosity, spheric index, erythrocyte surface area/erythrocyte volume) and lipid profile (total cholesterol, HDLP, LDLP, VLDLP cholesterol, triglycerides, beta-LP) were studied in 24 athletes aged 19-29 years. It is shown that athletes with a low atherogenic index (AI < 2.15) had lower viscosity of blood with standard hematocrit 45% and higher erythrocyte deformability compared to those in athletes with AI > 2.15. The correlation analysis detected positive correlation of erythrocyte suspension viscosity with AI, serum concentrations of triglycerides, beta-LP and negative correlation with concentrations of HDLP cholesterol. The value of the geometric factor of deformability correlated with concentration of VLDLP cholesterol and beta-LP. It is suggested that a close correlation exists between serum lipids and erythrocyte deformability.     

Comparative characteristics of fatty-acid composition of lipoproteins from human blood plasma and aortic wall

The fatty-acid composition of lipid fractions in lipoproteins of very low, low, and high density from blood plasma and the aortic wall of patients with atherosclerosis was investigated. A close similarity was found in the fatty-acid composition of phospholipids, triglycerides, and cholesterol esters in all classes of lipoproteins from the vascular wall and blood plasma. The composition of the fatty acids of the fractions was very similar in all classes of lipoproteins. Lipids from the vascular wall not included in the composition of lipoproteins differed considerably in their fatty-acid composition from lipids isolated from lipoproteins: the content of unsaturated fatty acids in the lipids of the aortic wall was much smaller than in lipoproteins.     

The vasoactive properties of different classes of blood lipoproteins in hypercholesterolemia and atherosclerosis

Studies were made of the effects of various classes of lipoproteins (LP) from the blood of rabbits with experimental hypercholesterolemia and human subjects with pronounced atherosclerosis on the vascular tone of rat thoracic aorta specimens. In hypercholesterolemia, there was a considerable weakening of a vasodilatory action of atherogenic LP fractions--LDL and VLDL. A vasodilatory effect of HDLP was not changed. In subjects suffering from atherosclerosis vasodilatory effects of both atherogenic and antiatherogenic HDLP decreased significantly. The revealed changes were related to shifts in lipid and protein components of LP complexes manifesting in the development of dyslipoproteinemia and dysapoproteinemia. In atherosclerosis accompanied with more profound changes suppression of vasodilatory effects of LP is greater than in transient experimental hypercholesterolemia. Consequently, changes of lipid and apo composition of LP and weakening of their vasodilatory action play a considerable role in the vessel tone changes in atherogenic situation.     

Cold-induced changes in blood lipoproteins in normotensive and hypertensive rats

It is shown that in thermoneutral conditions ISIAH (Inherited Stress-Induced Arterial Hypertension) hypertensive rats had a lower level of high-density lipoproteins (HDLP) in plasma and a higher atherogenic coefficient compared to normotensive Wistar rats. After cooling there were different changes in fractional composition of plasma lipoproteins both in normo- and hypertensive rats. These changes depended on the cooling rate and were more pronounced after slow cooling. Slow cooling resulted in a more significant increase of plasma HDLP and in a greater decrease in LDLP and atherogenic coefficient in hypertensive rats compared to normotensive ones.     

Hyperlipoproteinaemia and atherosclerosis in rabbits fed low-level cholesterol and lecithin

Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model, dietary lecithin promotes a return to normal of the LP distribution profile and removal of lipid from established atherosclerotic plaque.     

Hyperlipoproteinaemia and atherosclerosis in rabbits fed low-level cholesterol and lecithin.

Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model, dietary lecithin promotes a return to normal of the LP distribution profile and removal of lipid from established atherosclerotic plaque.     

Evidence for deficiency of high density lipoprotein lecithin: cholesterol acyltransferase activity (alpha-LCAT) in fish eye disease

In a rare familial condition, fish eye disease, there is a low relative content of cholesteryl esters in the plasma high density lipoproteins (HDL) but a normal content of these lipids in the very low (VLDL) and low (LDL) density lipoproteins. Lecithin: cholesterol acyltransferase (LCAT) is the enzyme which mediates the esterification of free cholesterol in the plasma lipoproteins. In the present investigation, isolated HDL from our two fish eye disease patients were found to be excellent substrates during in vitro incubations with normal LCAT as present in lipoprotein depleted plasma from control subjects. Almost all free cholesterol of these HDL fractions became esterified and concomitantly the abnormally small fish eye disease HDL particles increased to a size in the range of that of normal HDL particles. Lipoprotein depleted plasma from fish eye disease, however, lacked the property of normal plasma to esterify the free cholesterol of HDL isolated from plasma of fish eye disease patients or control subjects. These results have led to the formulation of a new concept implying that two different LCAT activities exist in normal plasma. One of these activities, denoted alpha-LCAT, is specific for HDL (alpha-lipoproteins) and the other, beta-LCAT, is specific for VLDL-LDL (pre beta- and beta-lipoproteins). Fish eye disease according to this notion is classified as an alpha-LCAT deficiency in contrast to the classical LCAT deficiency which probably lacks both alpha- and beta-LCAT activities.     

Different substrate specificities of plasma lecithin: cholesterol acyl transferase in fish eye disease and Tangier disease

Esterification of plasma free cholesterol is mediated by lecithin:cholesterol acyl transferase (LCAT). The free cholesterol of plasma high density lipoproteins (HDL) is considered to be the preferred substrate for LCAT. It therefore appeared as a paradox that plasma cholesterol esterification, both in vivo and in vitro, is normal in fish eye disease and Tangier disease, two familial conditions with extremely low plasma HDL levels. Fish eye disease plasma, however, was shown to have LCAT activity primarily acting on combined very low (VLDL) and low (LDL) density lipoproteins, denominated beta-LCAT, while it lacked LCAT activity esterifying HDL cholesterol (alpha-LCAT). Here we show that Tangier plasma, in contrast, has both alpha- and beta-LCAT. Thus, in both fish eye and Tangier diseases it is beta-LCAT that explains the apparent normal plasma cholesterol esterification. We also show that Tangier plasma, having alpha-LCAT activity, normalizes the low cholesteryl ester content as well as the abnormally small size of fish eye disease HDL particles during incubation.     

Cholesterol esterase activity in body fluids.

Antistreptolysin O activity (greater than or equal to 200 Todd units/ml) was found in 20% of 25 ascitic fluids, 20% of 55 pleural fluids and 37-5% of 56 joint fluids. These levels are not due to antibody but to the cholesterol moiety of altered beta-lipoproteins. The activity is precipitable with 10% dextran sulphate. Incubation of mixtures of fluids with titres less than 200 and normal human serum generated eight-fold or greater rises in antistreptolysin titres. This results from the activity of cholesterol esterase in the fluid acting on the beta-lipoprotein of the serum and activity was noted in 90% of ascitic fluids, 59% of pleural fluids and 54% of joint fluids. However, mixtures showing no such rise probably also contain esterase, the failure to demonstrate antistreptolysin activity being due to equilibration of ester derived cholesterol with sub-fractions of high density and very low density lipoproteins.     

Treatment of coronary heart disease by diet and exercise: Fasting and diurnal lipoproteins

Summary The effects of a combined exercise and low-fat dientary regimen were studied in 11 patients with angiographically documented coronary heart disease (cholesterol 233 mg/dl, triglycerides 158 mg/dl) and 13 comparable patients (cholesterol 224 mg/dl, triglycerides 174 mg/dl) on usual care. During one year, fasting serum lipoproteins were lowered to ideal levels in the intervention group (cholesterol 191 mg/dl, triglycerides 100 mg/dl, LDL-cholesterol 121 mg/dl). There was no change of triglycerides and cholesterol on usual care while LDL-cholesterol rose significantly. Neither regimen had any effect on HDL-cholesterol. Diurnal triglycerides as a presumptive measure of IDL in the intervention group were diminished by 39%. The study demonstrates the feasibility of a diet and exercise regimen to normalize midly elevated plasma lipid levels and thus to possibly affect the course of coronary heart disease without drugs.Abbreviations Chol cholesterol - TG triglycerides - HDL high density lipoproteins - LDL low density lipoproteins - LP(a) lipoprotein (a) - P/S polyunsaturated to saturated fatty acid ratio - Int. Intervention group - C Control group Supported by Bundesministerium für Forschung und Technologie     

Fractional Composition of Blood Serum Lipoproteins in Mice and Rats with Triton WR 1339-Induced Lipemia

We compared fractional composition of blood serum lipoproteins (LP) in female ICR mice and Wistar rats induced by single administration of a nonionic detergent Triton WR 1339 in doses of 300 and 500 mg/kg. Lipemia in animals of both species was characterized by a sharp increase in the concentration of cholesterol and, particularly, of triglycerides in blood serum lipoproteins by the 24th hour after administration of the detergent. We revealed a significant increase in the concentrations of atherogenic VLDL cholesterol (due to VLDL2), intermediate density lipoproteins, and LDL. These changes were more pronounced in rats. The model of lipemia can be used to study the role of fractional composition of lipoproteins and, particularly, of triglycerides in the pathogenesis of atherosclerosis. Moreover, this model holds much promise for evaluation of the efficiency of hypolipidemic drugs (statins and fibrates) in normalizing the increased level of atherogenic cholesterol of VLDL and LDL.     

Evidence for the presence in human plasma of lecithin: cholesterol acyltransferase activity (beta-LCAT) specifically esterifying free cholesterol of combined pre-beta- and beta-lipoproteins. Studies of fish eye disease patients and control subjects

The present study was undertaken to test our hypothesis that two different lecithin: cholesterol acyltransferase (LCAT) activities exist in normal human plasma, one denoted alpha-LCAT esterifying the free cholesterol of high density lipoproteins (HDL) and the other denoted beta-LCAT acting on the free cholesterol of very low (VLDL) and low (LDL) density lipoproteins. Plasmas depleted of HDL were obtained by means of preparative ultracentrifugation. Incubation at 37 degrees C of these plasma fractions from control subjects and patients with fish eye disease resulted in esterification of the remaining free cholesterol of combined VLDL and LDL (pre-beta- and beta-lipoproteins) in the HDL depleted plasmas. The shapes of the cholesterol esterification rate curves were similar for whole and HDL depleted plasmas from both control subjects and fish eye disease patients. In crosswise mixed incubation experiments with isolated combined VLD and LDL and total lipoprotein depleted plasma from a control subject and a patient with fish eye disease, respectively, esterification of free cholesterol occurred. Incubation of isolated total lipoproteins in plasma from a patient with LCAT deficiency mixed with total lipoprotein depleted plasma from a fish eye disease patient as a source of LCAT caused cholesterol esterification but did not result in normalization of the LCAT deficiency HDL particles, while the amount of normal-sized LDL particles increased. The present results support the hypothesis that a beta-LCAT exists in normal human plasma.     

Changes in plasma lipids and lipoprotein cholesterol during a high altitude mountaineering expedition (4800 m)

Summary Effects of high altitude exposure on plasma lipids and lipoprotein cholesterol were studied in 8 mountaineers who spent 3 weeks at the Annapurna IV base camp (4800 m) after a 12 day trek. In spite of the moderate physical exertion at the camp, the loss of body weight was more pronounced during the stay at high altitude than during the trekking period. Compared with baseline values observed at sea level, marked reductions in plasma cholesterol (–27%) and phospholipids (–19%) were found 3 days after arrival at the camp and persisted during the next 17 days. A less marked fall in plasma triglycerides occurred, weakly significant at the end of the stay. Because there were no relevant changes in very low density lipoproteins or in high density lipoprotein (HDL)-cholesterol, the low plasma cholesterol levels at the high altitude resulted mainly from the reduction in low density lipoprotein (LDL)-cholesterol: the mean HDL/LDL cholesterol ratio changed from 0.39 at sea level to 0.63 at the end of the stay at 4800 m. Fluctuations in LDL-cholesterol were not concomitant with those in body weight and were independent of the exercise training during the expedition. This study shows moreover that the early drop in LDL-cholesterol was associated with an opposite change in plasma levels of catecholamines and thyroid hormones. Taking into account that such hormonal responses are classically observed at high altitude, the concomitant decrease in LDL-cholesterol might be interpreted as being a relevant adaptative response to hypoxic conditions at high altitude.Abbreviations VLDL very low density lipoproteins - LDL low density lipoproteins - HDL high density lipoproteins     

Low density lipoprotein-containing circulating immune complexes and coronary atherosclerosis

Blood serum of most patients with coronary heart disease (CHD) caused a 2- to 5-fold increase in the lipid content of smooth muscle cells cultured from unaffected human aortic intima, i.e., possessed an atherogenic potential manifested in culture. Treatment of the CHD patients' serum with 2.5% polyethylene glycol 6000 removed the circulating immune complexes. The serum subjected to this treatment lost its atherogenic properties, i.e., failed to increase the content of lipids in cultured cells. Incubation of smooth muscle cells derived from human aortic intima with circulating immune complexes isolated from an atherogenic patient's serum caused a 1.5- to 3-fold rise in the intracellular cholesterol. Circulating immune complexes contained apolipoprotein B (apo B), but not apolipoproteins A1 and E. The apo B content strongly correlated with the total cholesterol content. The cholesterol/apo B ratio of the complexes was characteristic of low density lipoproteins (LDL), but not of very low density lipoproteins or intermediate density lipoproteins. The composition of the main lipid classes in these complexes was similar to that in LDL. Blood sera of most (90%) CHD patients was characterized by a high cholesterol and apolipoprotein B content in circulating immune complexes. The ability of these sera to induce lipid accumulation in cultured cells directly correlated with the cholesterol and apolipoprotein B level of circulating immune complexes (r = 0.91). These findings suggest that the atherogenic potential of CHD patients' blood serum is due to LDL-containing immune complexes.     

Evaluation of the classical methods for the diagnosis of type III hyperlipoproteinemia

Summary Familial type III hyperlipoproteinemia is characterized by the presence of elevated plasma levels of very low density lipoproteins (VLDL) which contain an increased amount of cholesterol and by the presence of a significant amount of lipoproteins with an intermediate density between that of VLDL and low density lipoproteins (LDL); the intermediate density lipoproteins, designated IDL or Lp III, have a slower electrophoretic migration rate than VLDL, and are found in the ultracentrifugal top fraction as a contaminant. Classically, the diagnosis of type III is based on the demonstration of beta-migrating lipoproteins in the ultracentrifugal top fraction (density <1.006), thus floating beta-lipoprotein. More recently, it has been proposed that an elevated VLDL-cholesterol to triglyceride ratio is diagnostic of the disorder. In the present report, we have compared the two methods for their diagnostic value and have concluded that the chemical index definition is the more reliable method for the diagnosis of type III hyperlipoproteinemia.     

Effect of exogenous lipids and lipoproteins on the primary immune response in vitro

Cholesterol and certain lipoproteins have regulatory effects on the primary immune responses of murine spleen cells in vitro. The plaque-forming cell (PFC) responses to sheep red blood cells of trinitrophenylated Brucella abortus were studied in complete, lipid-depleted or lipoprotein-reconstituted media. The requirement for exogenous low density lipoprotein (LDL) and its cholesterol moiety was established by comparison of the yield of PFC in cell cultures deprived of lipoproteins with that in cultures to which specific classes of lipoproteins were added. The spleen cells in complete medium yielded about 10-fold greater PFC responses than cells in lipoprotein-deficient medium. In lipoprotein-deficient media, human LDL completely reversed the decreased immune response, LDL lipids and free cholesterol partially reversed the deficit, the human high density lipoproteins and an apo B phospholipid complex were ineffective. In complete media, cholesterol at higher concentrations (100--200 microgram/ml) and LDL lipids partially inhibited the primary immune response. Exogenous cholesterol was required for the in vitro response to both thymus-dependent and thymus-independent antigens.     

Enhancement of normal polymorphonuclear cells respiratory burst in ascitic fluid by fibronectin. Comparison between cirrhotic and malignant ascitic fluids.

The chemiluminescence (CL) response of normal peripheral blood polymorphonuclear cells (PMN) in ascitic fluids (cirrhotic = 32; malignant = 17) was studied independently of the ascitic fluid complement activity. CL response and fibronectin levels were higher in malignant ascitic fluid than in cirrhotic ascitic fluid (p less than 0.001). Addition of pure fibronectin or malignant ascitic fluids to cirrhotic ascitic fluids increased the CL response of normal PMN. These findings suggest that the susceptibility of cirrhotic patients to spontaneous bacterial peritonitis (SBP) is a multifactorial defect involving factors distinct from low C3 levels. Fibronectin is an important factor in the promotion of the respiratory burst of normal PMN stimulated by opsonized zymosan or PMA in ascitic fluid. Our results suggest that low levels of ascitic fluid fibronectin could partly explain the high susceptibility of cirrhotic patients to spontaneous bacterial peritonitis.     

The Fate of Intravenously Administered Radioactive Cholesterol Dispersion in the Rat

The present work was aimed at studying the first stages of disappearance of particulate cholesterol from the circulation. The distribution of radioactivity in blood, liver, spleen, lungs and kidneys was determined at different time intervals after i.v. injections of aqueous-ethanolic dispersions of radioactive cholesterol to rats. More than 95% of the dose disappeared from the circulation in 10 min. From 71 to 93% of the dose was found in the liver 5 min-2 h after the injection. According to autoradiography, most of the particulate cholesterol was immediately taken up by the liver parenchymal cells. There were only few grains over the Kupffer cells. 2 min to 6 h after the injection the highest specific radioactivity was in the free cholesterol fraction of the liver. The specific activity of liver esterified cholesterol was 54 % of that of the free cholesterol at 1 h. They both declined gradually and reached the same level in 1–2 days. There was a gradual rise of the specific activities of plasma free and esterified cholesterol starting 30 min after the injection. Both reached a maximum in 6–16 h, when the curve of plasma esterified cholesterol intersected that of liver esterified cholesterol. The radioactivity reappearing in plasma was associated with lipoproteins and red cells; the cholesterol of the high density lipoproteins had the highest specific activity. The results indicate that particulate cholesterol is taken up chiefly by the parenchymal cells of the liver and is subsequently incorporated into the plasma lipoproteins, most rapidly into the high density lipoproteins. A large fraction of plasma esterified cholesterol originates in the liver.     

Separation of bovine plasma lipoproteins by a rapid ultracentrifugation method

The recently described method of centrifugation with iodixanol for the rapid separation of human plasma lipoproteins was adapted to separate bovine plasma lipoproteins. Density gradients were generated by mixing plasma with iodixanol 12% (w/v), followed by centrifugation at 350,000 g and 16 degrees C for 3 h 10 min in a vertical rotor. Gradients were unloaded dense-end first into 10 fractions. Human very low density lipoprotein (VLDL; density < 1.011 g/ml), low density lipoprotein (LDL; density = 1.016-1.039 g/ml) and high density lipoprotein (HDL; density = 1.039-1.090 g/ml) were resolved well at densities considerably lower than those traditionally reported in salt gradients. In gradients generated from 12% iodixanol, bovine LDL and HDL exhibited even lower densities (1.016-1.028 and 1.016-1.048 g/ml, respectively) with all lipoproteins occurring at the lower density region of the gradient. In contrast, density gradients generated from layers of equal volumes of 6% and 12% iodixanol readily separated bovine HDL from VLDL, whilst LDL still overlapped with HDL. The latter accounts for >80% of all bovine lipoproteins and exists as two populations, namely light and heavy HDL. Gradients generated from two layers of iodixanol recovered bovine HDL in five fractions. The hypercholesterolaemia associated with lactation resulted in a modest shift in the profile of HDL cholesterol towards lipoprotein particles of lower density (light HDL). Significant between-farm differences were also detected in the density profiles of bovine plasma cholesterol. This new method is suitable for use in research and diagnosis in relation to lipoprotein metabolism disorders in cows.     

Serum lipids and proteins in newborn infants in Ivory Coast

This study has permitted, from samples of the cord of 521 newborns in the Ivory Coast, to determine the average values of the following blood parameters: total proteins, total cholesterol, triglycerides, uric-acid, natrium, high density lipoproteins (HDL), very low density lipoproteins (VLDL), low density lipoproteins (LDL), HDL cholesterol (HDLC), VLDL cholesterol (VLDL-C), LDL cholesterol (LDLC), albumin, alpha 1, alpha 2, beta and gammaglobulins. Variations of the biochemical parameters in function of sex, social standard and races, as well as the correlations between the lipidic and protidic parameters were set forth.