Effect of sleep deprivation on cholesterol metabolism and triglyceridaemia in male volunteers

The effect of 5-day sleep deprivation (SD) on cholesterol metabolism, together with triglyceridaemia, was studied in seven healthy male volunteers. A 3-day control period was followed by 5 days (120 h) complete SD and 4 days recovery. Blood was collected at 9 a.m. and at 9 p.m. Vastus lateralis muscle biopsy was performed during the control period, on the 5th day of SD, and on day 3 of recovery. The value of muscle cholesterol was related to the non-collagen protein content. The plasma triglycerides (TG) varied in a circadian biorhythm, the amplitude of which declined gradually during SD. The morning triglyceridaemia was significantly decreased on days 3-5 of SD (35%-79% of initial values). On days 4 and 5 of SD, plasma cholesterol fell significantly to 78% and 88% of control values, respectively. The ratio of its esterified to unesterified fractions remained unchanged throughout SD. Basal activity of lecithin cholesterol acyltransferase (LCAT) showed no diurnal biorhythm; on the last 2 days of SD, LCAT activity fell significantly to 71%-80%. In contrast, the decrease in fractional esterification rate (FER) was insignificant. In the vastus lateralis muscle, total cholesterol (TC) was decreased by 40% at the end of SD, the reduction being greater for cholesterol esters (CE) (by 63%) than for free cholesterol (FC) (by 36%). The relative proportion of CE significantly decreased from an initial 14.7% to 9.2% on the last day of SD. During recovery after SD, plasma cholesterol and TG slowly returned to normal. LCAT activity and FER recovered quickly, within 48 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fractional cholesterol esterification rate and muscle cholesterol of healthy young men

A group of fourteen healthy young male volunteers was examined to define more exactly the relations between lecithin cholesterol acyltransferase activity (LCAT), fractional cholesterol esterification rate (FER), total cholesterol (TC) and its free and esterified fractions (FC, CE) in skeletal muscles under physiological conditions. The mean values (+/- S.D.) of LCAT activity (95.4 +/- 16.3 mumol .1(-1) per hour), and FER (7.45 +/- 1.54% per hour) corresponded to published data on normolipidaemic healthy men of normal body weight. The mean value of TC in muscles was 332 +/- 83 micrograms per 100 mg of non-collagen protein, of which 14 +/- 7.4 per cent was formed by cholesterol esters. There was positive correlation between TC in muscles and age. Significant positive correlations between FER and the content of esterified cholesterol in muscles, and between FER and the proportion of esterified to total muscle cholesterol were found. These results suggest a close interrelation of cholesterol ester metabolism in the plasma and in slow pool tissues.     

Factors influencing the cholesterol esterification rate in lecithin cholesterol acyltransferase radioassay

Factors affecting the esterification rate of cholesterol by lecithin cholesterol acyltransferase (LCAT E.C. 2.3.1.43) in native cold labelled substrates (human, rabbit, rat serum, plasma, VLDL, LDL depleted serum, rabbit intraocular fluids) repaired by use of ready-made 14C-cholesterol discs (Cholesterol kinetics LCAT-test, UVVVR, Czechoslovakia) were investigated. EDTA added to the serum during the cold incubation (18 h, 0 degrees C-4 degrees C) increased the rate of esterification due to elimination of Ca2+ ions. The similar stimulating effect was found in the presence of mercaptoethanol (ME) in the serum, while in the plasma already stimulated by EDTA no additional effect by ME could be noticed. Freezing and thawing did not affect the fractional esterification rate (FER-per cent of total serum unesterified cholesterol esterified per hour) in normolipidaemic sera, whereas in hyperlipidaemic sera, particularly those with high levels of VLDL, FER was stimulated. Esterification partially proceeded during the cold incubation of serum or plasma with 14C-cholesterol ready-to-use discs, attaining the values of about 0.3%/h and 2-6%/h, respectively, in human sera and in rabbit and rat sera. The starting level of esterification did not affect the linearity of LCAT reaction during warm incubation (30 min at 37 degrees C), neither was the absolute value of FER changed as compared with cold labelled sera with those inhibited by DTNB and reactivated by ME. Substantial LCAT activity was also detected in extremely diluted substrates--such as intraocular fluid collected from rabbits with induced uveitis or after preceding paracentesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of labeling of plasma lipoproteins with [(3)H]cholesterol on values of esterification rate of cholesterol in apolipoprotein B-depleted plasma

The fractional esterification rate of cholesterol in apolipoprotein B (apoB)-depleted plasma (FER(HDL)) is a good indicator of particle size distribution in high density lipoprotein (HDL) and low density lipoprotein (LDL). However, there has been a discrepancy in the absolute values of FER(HDL) published by different laboratories. Because the main difference between the methods was in the labeling of lipoproteins with [(3)H]cholesterol we investigated the effect of using Corning immunoplates and paper discs as carriers of the labeled unesterified cholesterol. We found that Corning plates trap some (3)H-labeled free cholesterol, which is released during incubation at 37 degrees C. This means that this additional (3)H-labeled free cholesterol is exposed to lecithin: cholesterol acyltransferase (LCAT) for a shorter time and artificially decreases FER(HDL). Using paper discs discarded before incubation as carriers of the (3)H-labeled free cholesterol results in complete labeling of HDL and thus yields higher values of FER(HDL).     

Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk

Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. LCAT is a major factor in HDL remodeling and metabolism, and it has long been believed to play a critical role in macrophage reverse cholesterol transport (RCT). The effect of LCAT on human atherogenesis is still controversial. In the present study, the plasma LCAT concentration was measured in all subjects (n = 540) not on drug treatment at the time of enrollment in the multicenter, longitudinal, observational IMPROVE study. Mean and maximum intima-media thickness (IMT) of the whole carotid tree was measured by B-mode ultrasonography in all subjects. In the entire cohort, LCAT quartiles were not associated with carotid mean and maximum IMT (P for trend 0.95 and 0.18, respectively), also after adjustment for age, gender, HDL-cholesterol (HDL-C), and triglycerides. No association between carotid IMT and LCAT quartiles was observed in men (P=0.30 and P=0.99 for mean and maximum IMT, respectively), whereas carotid IMT increased with LCAT quartiles in women (P for trend 0.14 and 0.019 for mean and maximum IMT, respectively). The present findings support the concept that LCAT is not required for an efficient reverse cholesterol transport and that a low plasma LCAT concentration and activity is not associated with increased atherosclerosis.     

Apolipoprotein AIMilano. Partial lecithin:cholesterol acyltransferase deficiency due to low levels of a functional enzyme

The cholesterol esterification process was analyzed in 19 carriers of the apolipoprotein AIMilano (AIM) variant and in 19 age-sex matched controls by measuring lecithin:cholesterol acyltransferase (LCAT) mass, activity (i.e., cholesterol esterification with a standard proteoliposome substrate) and cholesterol esterification rate (i.e., cholesterol esterification in the presence of the endogenous substrate). The AIM subjects had lower LCAT mass (3.30 +/- 0.85 micrograms/ml), activity (71.1 +/- 36.4 nmol/ml per h) and cholesterol esterification rate (23.6 +/- 12.5 nmol/ml per h) compared to controls (5.22 +/- 0.74 micrograms/ml, 121.6 +/- 54.6 nmol/ml per h and 53.6 +/- 29.9 nmol/ml per h, respectively). The specific LCAT activity, i.e., LCAT activity per microgram of LCAT, was similar in the two groups, indicating that the LCAT protein in the AIM carriers is structurally and functionally normal. However, the specific cholesterol esterification rate was 23% lower in the AIM subjects (8.03 +/- 6.01 nmol/h per microgram) compared to controls (10.49 +/- 5.86 nmol/h per microgram; P less than 0.05). The capacity of HDL3, purified from both AIM and control plasma, to act as substrates for cholesterol esterification was similar, thus suggesting that other mechanism(s) may be in play. Carriers with a relative abundance of abnormal, small HDL3b particles had the most altered cholesterol esterification pattern. Upon evaluating all AIM subjects, a complex relationship between HDL structure, plasma lipid-lipoprotein levels and cholesterol esterification emerged, making the AIMilano condition a unique model for the study of the mechanisms regulating the cholesterol esterification-transfer process in man.     

Cholesterol esterification by lecithin-cholesterol acyltransferase in A-I-free plasma

Lecithin-cholesterol acyltransferase (LCAT) mass, activity and endogenous cholesterol esterification rate were measured in plasma and apolipoprotein A-I-free (A-I-free) plasma from two normolipidemic and two hyperlipidemic subjects, and from a patient with Tangier disease. A-I was removed from plasma by an anti-A-I immunosorbent. LCAT activity was measured using an exogenous substrate. The plasma LCAT concentration of the four non-Tangier subjects was 4.63 +/- 0.64 micrograms/ml (mean +/- S.D.); means of 26 +/- 7% of total LCAT mass and 22 +/- 11% of plasma LCAT activity were found in their A-I-free plasma. The plasma LCAT concentration of the Tangier subject was 1.49 micrograms/ml. About 95% of LCAT mass and all LCAT activity were found in the A-I-free plasma. Thus, the LCAT mass (1.4 micrograms/ml) and activity (43.1 nmol/h per ml) in Tangier A-I-free plasma were not significantly different from that found in the four non-Tangier A-I-free plasmas (mass = 1.21 +/- 0.44 micrograms/ml; activity: 27.3 +/- 18.4 nmol/h per ml). Although the LCAT activity per unit mass of the enzyme in plasma and A-I-free plasma were comparable (24.9 +/- 2.8 vs. 22.8 +/- 7.8 nmol/h per micrograms LCAT, n = 5), the plasma cholesterol esterification rate of A-I-free plasma from all subjects was lower than that found in plasma (7.5 +/- 2.7 vs. 13.0 +/- 3.8 nmol/h per micrograms LCAT). In conclusion, although A-I-containing lipoproteins are the preferred substrates of LCAT, other LCAT substrates and cofactors are found in A-I-free plasma along with LCAT. Thus, non-A-I-containing particles can serve as physiological substrates for cholesterol esterification mediated by LCAT.     

Opposite regulation of hepatic lipase and lecithin: cholesterol acyltransferase by glucocorticoids in rats.

Rats were treated with hydrocortisone, dexamethasone or triamcinolone for 4 days. The effect of treatment on hepatic lipase and lecithin:cholesterol acyltransferase (LCAT) mRNA levels and catalytic activities was determined. Hepatic lipase mRNA was not affected by hydrocortisone, but was decreased after dexamethasone (-28%) and triamcinolone (-54%). Hepatic lipase activity followed the same pattern, it was not affected by hydrocortisone and lowered by dexamethasone (-38%) and triamcinolone (-70%). The LCAT mRNA level in the liver was also not affected by hydrocortisone, but increased upon treatment with dexamethasone (+22%) and triamcinolone (+72%). Plasma LCAT, determined with an excess exogenous substrate (designated LCAT-II), tended to decrease after hydrocortisone treatment (-11%) and was higher after dexamethasone (+21%) and triamcinolone (+22%). The plasma cholesterol esterification rate (designated LCAT-I), determined by incubation of the plasma at 37 degrees C, followed the same pattern. The activity ratio of hepatic lipase/LCAT-II decreased from 1 in the controls to 0.51 after dexamethasone and 0.25 in the triamcinolone-treated animals. The plasma HDL cholesterol concentration in the different groups changed oppositely to the hepatic lipase/LCAT activity ratio. It is concluded that HDL cholesterol is raised by synthetic glucocorticoids due, among other factors, to a lowered hepatic lipase and an increased plasma LCAT activity. The influence of glucocorticoids on these enzymes is, at least partly, explained by the effects on the hepatic mRNA contents.     

Relations between particle size of HDL and LDL lipoproteins and cholesterol esterification rate

Particle size of low density (LDL) and high density (HDL) lipoproteins and cholesterol esterification rate in HDL plasma (FER(HDL)) are important independent predictors of coronary artery diseases (CAD). In this study we assessed the interrelations between these indicators and routinely examined plasma lipid parameters and plasma glucose concentrations. In 141 men, healthy volunteers, we examined plasma total cholesterol (TC), triglycerides (TG), HDL and LDL cholesterol (HDL-C, LDL-C) and HDL unesterified cholesterol (HDL-UC). Particle size distribution in HDL and LDL was assessed by gradient gel electrophoresis and FER(HDL) was estimated by radioassay. An effect of particle size and FER(HDL) on atherogenic indexes as the Log(TG/HDL-C) and TC/HDL-C was evaluated. Subjects in the study had plasma concentrations (mean +/- S.D.) of TC 5.2+/-0.9 mmol/l, HDL-C 1.2+/-0.3 mmol/l, TG 2.1+/-1.7 mmol/l, glucose 5+/-0.8 mmol/l. Relative concentration of HDL(2b) was 17.6+/-11.5 % and 14.6+/-11.8 % of HDL(3b,c). The mean diameter of LDL particles was 25.8+/-1.5 nm. The increase in FER(HDL) significantly correlated with the decrease in HDL(2b) and LDL particle size (r = -0.537 and -0.583, respectively, P<0.01) and the increase in HDL(3b,c) (0.473, P<0.01). Strong interrelations among TG and HDL-C or HDL-UC and FER(HDL) and particle size were found, but TC or LDL-C did not have such an effect. Atherogenic indexes Log(TG/HDL-C) and TC/HDL-C correlated with FER(HDL) (0.827 and 0.750, respectively, P<0.0001) and with HDL and LDL particle size.     

Effect of growth hormone replacement therapy on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults

The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, are unknown. We carried out a 6 months study in 24 GH-deficient adults who were randomized to placebo (n = 8), low dose GH (1 U daily, n = 8), and high dose GH (2 U daily, n = 8), followed by a 6 months open extension study with high dose GH (1 drop-out). No significant changes in plasma lipoproteins, LCAT, CETP, and PLTP activities, cholesterol esterification (EST) and cholesteryl ester transfer (CET) were observed after placebo. After 6 months of GH (combined data, n = 24), very low + low density lipoprotein (VLDL + LDL) cholesterol (P < 0.05) and apolipoprotein B (P < 0.05) decreased, whereas HDL cholesterol and HDL cholesteryl ester increased (P < 0. 05). Prolonged treatment showed comparable effects. Plasma apolipoprotein A-I and Lp[a] remained unchanged. Plasma LCAT (P < 0. 01) and CETP activities (P < 0.01), as well as EST (P < 0.01) and CET decreased (P < 0.01) after 12 months of GH (n = 15), but PLTP activity did not significantly change. Changes in EST and CET after 12 months of treatment were independently related to changes in plasma LCAT (P = 0.001 and CETP activity (P = 0.01). In conclusion, GH replacement therapy improves the lipoprotein profile in GH-deficient adults. Chronic GH replacement lowers plasma LCAT and CETP activities, contributing to a decrease in cholesterol esterification and cholesteryl ester transfer. These effects may have consequences for HDL metabolism and reverse cholesterol transport.     

Cholesterol esterification and atherogenic index of plasma correlate with lipoprotein size and findings on coronary angiography

We examined the association between rate of cholesterol esterification in plasma depleted of apolipoprotein B-containing lipoproteins (FER(HDL)), atherogenic index of plasma (AIP) [(log (TG/HDL-C)], concentrations, and size of lipoproteins and changes in coronary artery stenosis in participants in the HDL-Atherosclerosis Treatment Study. A total of 160 patients was treated with simvastatin (S), niacin (N), antioxidants (A) and placebo (P) in four regimens. FER(HDL) was measured using a radioassay; the size and concentration of lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. The S+N and S+N+A therapy decreased AIP and FER(HDL), reduced total VLDL (mostly the large and medium size particles), decreased total LDL particles (mostly the small size), and increased total HDL particles (mostly the large size). FER(HDL) and AIP correlated negatively with particle sizes of HDL and LDL, positively with VLDL particle size, and closely with each other (r = 0.729). Changes in the proportions of small and large lipoprotein particles, which were reflected by FER(HDL) and AIP, corresponded with findings on coronary angiography. Logistic regression analysis of the changes in the coronary stenosis showed that probability of progression was best explained by FER(HDL) (P = 0.005). FER(HDL) and AIP reflect the actual composition of the lipoprotein spectrum and thus predict both the cardiovascular risk and effectiveness of therapy. AIP is already available for use in clinical practice as it can be readily calculated from the routine lipid profile.     

Understanding the mechanism of LCAT reaction may help to explain the high predictive value of LDL/HDL cholesterol ratio.

Traditionally, lecithin:cholesterol acyltransferase (LCAT) role in the reverse cholesterol transport (RCT) has been considered "antiatherogenic" as the cholesterol esterification is the prerequisite for the formation of mature high density lipoprotein (HDL) particles and may create a gradient necessary for the flow of unesterified cholesterol (UC) from tissues to plasma. However, newer data suggest that a higher esterification rate is not necessarily protective. Here we review the available data on the role of LCAT in RCT and propose that the LCAT-mediated esterification of plasma cholesterol promotes RCT only in the presence of sufficient concentrations of HDL2 while this reaction may be atherogenic in the presence of high concentration of plasma low density lipoprotein (LDL) cholesterol Thus, the "protective" or potentially "atherogenic" role of LCAT depends on the quality of HDL and concentration of LDL. This hypothesis is consistent with the known high predictive value of LDL/HDL cholesterol ratio.     

Lecithin:cholesterol acyltransferase regulation. II. Effect of fluidity of egg phosphatidylcholine vesicles

The regulation of human plasma lecithin:cholesterol acyltransferase (LCAT) by changes in bilayer fluidity of substrate egg phosphatidylcholine (egg PC) unilamellar vesicles was investigated using pyrene excimer fluorescence to measure fluidity. Fluidity was decreased by adding up to 20% cholesterol or increased by adding up to 10% egg 2-lysophosphatidylcholine (lysoPC). The fluidizing effect of lysoPC was suppressed by the addition of cholesterol. LCAT activity with 10% cholesterol vesicles was decreased by adding 5% lysoPC, yet activity with 5% cholesterol vesicles was unaffected by adding 5% lysoPC. This difference may be explained by a balance between the known LCAT inhibitory effect of lysoPC and its ability to increase bilayer fluidity and thereby increase LCAT activity. LCAT esterification of up to 37% of vesicle cholesterol failed to alter the lysoPC/cholesterol balance sufficiently to influence activity in this system. The findings of our studies are in keeping with modulation of LCAT activity by bilayer fluidity, but fluidity changes caused by enzyme action are not sufficient to regulate that activity.     

Isolation and properties of porcine lecithin:cholesterol acyltransferase

Lecithin: cholesterol acyltransferase (LCAT, phosphatidylcholine: sterol O-acyltransferase, EC 2.3.1.43) was purified approximately 20 000-fold from pig plasma by ultracentrifugation, phenyl-Sepharose and hydroxyapatite chromatography. Purified LCAT had an apparent relative molecular mass of 69 000 +/- 2000. By isoelectrofocusing it separated into five or six bands with pI values ranging from pH 4.9 to 5.2. The amino acid composition was similar to that of the human enzyme. An antibody against pig LCAT was prepared in goat. The antibody reacted against pig LCAT and gave a reaction of partial identity with human LCAT. Incubation of pig plasma or purified enzyme with the antibody virtually inhibited LCAT activity. The same amount of antibody inactivated only 62% of the LCAT activity in human serum. Pig and human LCAT were activated to the same extent by either human or pig apolipoprotein A-I (apo-A-I) using small liposomes as substrate. Human apoA-I, however, caused a higher esterification rate for both enzymes. Using apoA-I and small liposomes as a substrate, the addition of apoC-II up to 4 micrograms/ml had no effect on the LCAT reaction, but above this concentration LCAT was inhibited. Small liposomes with phosphatidylcholine/cholesterol molar ratios of 3:1 up to 8.4:1 did not show any significant differences in the LCAT reaction, when used as substrates in the presence of various amounts of apoA-I and albumin. In contrast, the LCAT activity was significantly reduced by liposomes with phosphatidylcholine/cholesterol molar ratios below 3:1.     

Reactivity of HDL subfractions towards lecithin-cholesterol acyltransferase. Modulation by their content in free cholesterol

(1) Human HDL2 (d 1.070-1.125) and HDL3 (d 1.125-1.21) labelled with unesterified [14C]cholesterol, were incubated with a source of lecithin-cholesterol acyltransferase. For optimal activity, the reaction required the addition of albumin in excess, at least 3-times greater than the concentration of HDL-free cholesterol. Under such conditions, the reaction appeared saturable. HDL3 was found the most efficient substrate and the Vmax values expressed for 1.5 IU LCAT/ml and with an albumin/free cholesterol ratio of 3, were 8.3 nmol free cholesterol esterified/ml per h and 4.1 nmol/ml per h for HDL3 and HDL2, respectively. (2) HDL3 were modified in the presence of VLDL by inducing triacylglycerol lipolysis with a semipurified lipoprotein lipase from bovine milk. The newly formed HDL had gained free cholesterol and phospholipids, so that about 50% of these modified HDL, referred to as light-LIP-HDL3, were reisolated in the HDL2 density range. Light-LIP-HDL3 were enriched mostly in free cholesterol (+ 160%) and in phospholipid (+ 40%). Their reactivity towards LCAT was half-reduced compared to parent HDL3, which correlated well with a decrease in their phospholipid/free cholesterol molar ratio. Moreover, HDL3 artificially enriched in free cholesterol and exhibiting a comparable PL/FC behaved like lipolysis-modified HDL in their reactivity towards LCAT. (3) HDL3 were also modified by co-incubation with VLDL (post-VLDL-HDL3), or with VLDL and a source of lipid transfer protein (CET-HDL3). The latter treatment greatly affected the lipid composition of the core particle (-25% esterified cholesterol, +190% TG). In both cases, the moderate decreasing LCAT reactivity observed could be related to the phospholipid/free cholesterol ratio. Thus, like in artificial substrates, the lipid composition of the HDL surface may control the rate of LCAT-mediated cholesterol esterification.     

A fluorescence method to detect and quantitate sterol esterification by lecithin:cholesterol acyltransferase

We describe a simple but sensitive fluorescence method to accurately detect the esterification activity of lecithin:cholesterol acyltransferase (LCAT). The new assay protocol employs a convenient mix, incubate, and measure scheme. This is possible by using the fluorescent sterol dehydroergosterol (DHE) in place of cholesterol as the LCAT substrate. The assay method is further enhanced by incorporation of an amphiphilic peptide in place of apolipoprotein A-I as the lipid emulsifier and LCAT activator. Specific fluorescence detection of DHE ester synthesis is achieved by employing cholesterol oxidase to selectively render unesterified DHE nonfluorescent. The assay accurately detects LCAT activity in buffer and in plasma that is depleted of apolipoprotein B lipoproteins by selective precipitation. Analysis of LCAT activity in plasmas from control subjects and sickle cell disease (SCD) patients confirms previous reports of reduced LCAT activity in SCD and demonstrates a strong correlation between plasma LCAT activity and LCAT content. The fluorescent assay combines the sensitivity of radiochemical assays with the simplicity of nonradiochemical assays to obtain accurate and robust measurement of LCAT esterification activity.     

Atherogenic lipoprotein profile in families with and without history of early myocardial infarction

In this study we compared several parameters characterizing differences in the lipoprotein profile between members of families with a positive or negative family history of coronary artery disease (CAD). In addition to regular parameters such as the body mass index (BMI), total plasma cholesterol (TC), low density (LDL-C) and high density (HDL-C) cholesterol and triglycerides (TG) we estimated the fractional esterification rate of cholesterol in apoB lipoprotein-depleted plasma (FER(HDL)) which reflects HDL and LDL particle size distribution. A prevalence of smaller particles for the atherogenic profile of plasma lipoproteins is typical. Log (TG/HDL-C) as a newly established atherogenic index of plasma (AIP) was calculated and correlated with other parameters. The cohort in the study consisted of 29 young (< 54 years old) male survivors of myocardial infarction (MI), their spouses and at least one offspring (MI group; n=116). The control group consisted of 29 apparently healthy men with no family history of premature CAD in three generations, their spouses and at least one offspring (control group; n=124). MI families had significantly higher BMI than the controls, with the exception of spouses. Plasma TC did not significantly differ between MI and the controls. MI spouses had significantly higher TG. Higher LDL-C had MI survivors only, while lower HDL-C had both MI survivors and their spouses compared to the controls. FER(HDL) was significantly higher in all the MI subgroups (probands 25.85+/-1.22, spouses 21.55+/-2.05, their daughters 16.93+/-1.18 and sons 19.05+/-1.33 %/h) compared to their respective controls (men 20.80+/-1.52, spouses 14.70+/-0.98, daughters 13.23+/-0.74, sons 15.7+/-0.76 %/h, p<0.01 to p<0.05). Log(TG/HDL-C) ranged from negative values in control subjects to positive values in MI probands. High correlation between FER(HDL) and Log (TG/HDL-C) (r=0.80, p<0.0001) confirmed close interactions among TG, HDL-C and cholesterol esterification rate. The finding of significantly higher values of FER(HDL) and Log (TG/HDL-C) indicate higher incidence of atherogenic lipoprotein phenotype in members of MI families. The possibility that, in addition to genetic factors, a shared environment likely contributes to the familial aggregation of CAD risk factors is supported by a significant correlation of the FER(HDL) values within spousal pairs (control pairs: r=0.51 p<0.01, MI pairs: r=0.41 p<0.05).     

Influence of acute maximal exercise on lecithin:cholesterol acyltransferase activity in healthy adults of differing aerobic performance

To document the possible influence of a single episode of maximal aerobic stress on the serum lecithin:cholesterol acyltransferase (LCAT) activity in subjects with differing histories of training, two groups of healthy male adults [controls (C), n = 18, 28.6 years, SD 5.2, 50.1 ml.kg-1.min-1 maximal O2 uptake (VO2max), SD 5.3; endurance trained athletes (T), n = 18, 31.4 years, SD 8.8, 65.0 ml.kg-1.min-1 VO2max, SD 2.8] were examined in a maximal aerobic stress test. In addition to the routine assessment of lipid status, LCAT activity was measured immediately before and after exercise. At rest nearly identical LCAT activity values were found in both groups: C 64.4 nmol.ml-1.h-1, SD 16.7 vs T 65.0 nmol.ml-1.h-1, SD 20.9. The post-exercise LCAT values induced by the maximal stress test increased significantly to (C) 95.7 nmol.ml-1.h-1, SD 23.5, +48.6%, P less than 0.001; (T) 83.5 nmol.ml-1.h-1, SD 24.3, +29.1%, P less than 0.01. Neither the pre nor the postexercise individual LCAT activity values showed any significant correlation to the corresponding data on physical performance.     

Serum lipoproteins and albumin in the lecithin: Cholesterol acyltransferase reaction

The unique features of pig ovarian follicular fluids, i.e., presence of high density lipoprotein (HDL) only and lecithin: cholesterol acyltransferase (EC 2.3.1.43; LCAT) activity, provides a good model to study the effect of serum lipoproteins and serum albumin on the LCAT reaction. $\text{In}\text{vitro}$ cholesterol esterification is enhanced when very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions are added, but is inhibited when one or the other of these lipoproteins is absent. High concentrations of HDL₂ result in decreased activation which can be compensated for by the addition of the VLDL-LDL mixture. These findings suggest that the rate of cholesterol esterification in ovarian follicular fluid may be enhanced by providing the exogenous VLDL and LDL as the recipients of HDL-cholesteryl ester. The inhibition of LCAT activity caused by free fatty acid and lysophosphatidylcholine can be partially reversed by the addition of serum albumin, suggesting that serum albumin may regulate the LCAT reaction.     

Association of metabolic and genetic factors with cholesterol esterification rate in HDL plasma and atherogenic index of plasma in a 40 years old Slovak population

We assessed association between novel biomarkers of cardiovascular disease and conventional factors in 40 years old subjects (208 men and 266 women) from the general population of Slovakia. FER(HDL) (cholesterol esterification rate in HDL plasma), AIP--Atherogenic Index of Plasma [Log(TG/HDL-C)] as markers of lipoprotein particle size, and CILP2, FTO and MLXIPL polymorphisms, were examined in relation to biomarkers and conventional risk factors. Univariate analyses confirmed correlation between AIP, FER(HDL) and the most of measured parameters. Relations between AIP and CILP2, FTO and MLXIPL were not significant. However, CILP2 was significantly related to FER(HDL) in both genders. In multivariate analysis BMI was the strongest correlate of AIP levels. In multivariate model variability of FER(HDL) was best explained by AIP (R(2) = 0.55) in both genders with still significant effect of CILP2 SNP in men. In a model where AIP was omitted, TG levels explained 43 % of the FER(HDL) variability in men, while in women HDL-C was the major determinant (42 %). In conclusions, FER(HDL) and AIP related to the known markers of cardiovascular risk provide means to express their subtle interactions by one number. Our novel finding of association between CILP2 polymorphism and FER(HDL) supports its role in lipid metabolism.