Atherogenic impact of lecithin-cholesterol acyltransferase and its relation to cholesterol esterification rate in HDL (FER(HDL)) and AIP [log(TG/HDL-C)] biomarkers: the butterfly effect?

The atherogenic impact and functional capacity of LCAT was studied and discussed over a half century. This review aims to clarify the key points that may affect the final decision on whether LCAT is an anti-atherogenic or atherogenic factor. There are three main processes involving the efflux of free cholesterol from peripheral cells, LCAT action in intravascular pool where cholesterol esterification rate is under the control of HDL, LDL and VLDL subpopulations, and finally the destination of newly produced cholesteryl esters either to the catabolism in liver or to a futile cycle with apoB lipoproteins. The functionality of LCAT substantially depends on its mass together with the composition of the phospholipid bilayer as well as the saturation and the length of fatty acyls and other effectors about which we know yet nothing. Over the years, LCAT puzzle has been significantly supplemented but yet not so satisfactory as to enable how to manipulate LCAT in order to prevent cardiometabolic events. It reminds the butterfly effect when only a moderate change in the process of transformation free cholesterol to cholesteryl esters may cause a crucial turn in the intended target. On the other hand, two biomarkers - FER(HDL) (fractional esterification rate in HDL) and AIP [log(TG/HDL-C)] can offer a benefit to identify the risk of cardiovascular disease (CVD). They both reflect the rate of cholesterol esterification by LCAT and the composition of lipoprotein subpopulations that controls this rate. In clinical practice, AIP can be calculated from the routine lipid profile with help of AIP calculator www.biomed.cas.cz/fgu/aip/calculator.php.

[AIP--atherogenic index of plasma as a significant predictor of cardiovascular risk: from research to practice]. / AIP--aterogenní index plazmy jako významný prediktor kardiovaskulárního rizika: od výzkumu do praxe.

BACKGROUND: Various indices have been used for the diagnosis and prognosis of cardiovascular disease (CVD). Atherogenic index of plasma (AIP) is a logarithmically transformed ratio of molar concentrations of triglycerides to HDL-cholesterol. The strong correlation of AIP with lipoprotein particle size may explain its high predictive value. Here we summarize data on AIP calculated in 8394 subjects from 6 population and clinical studies. RESULTS: AIP values increase with increasing CV risk. Thus umbilical cord, young children, healthy women have values below 0.1 while men and subjects with CV risk factors such as hypertension, diabetes, dyslipidemia have increasing values up to 0.4. Based on these data we suggest that AIP values of -0.3 to 0.1 are associated with low, 0.1 to 0.24 with medium and above 0.24 with high CV risk. In the population study men had higher AIP values than women. In a cohort undergoing coronary angiography AIP, in model that included age, BMI, waist circumference, type 2. DM, blood pressure, smoking, TG, TC, LDL-C, apoB, HDL-C, and TC/HDL-C, AIP was the best predictor of positive findings. AIP was also a highly sensitive marker of differences of lipoprotein profiles in families of patients with premature myocardial infarction and control families. Treatment with ciprofibrate, and combination of statin and niacin dramatically decreased AIP. Combination with hypoglycemic therapy that included pioglitazone decreased AIP in patiens with type 2. diabetes. CONCLUSIONS: AIP can be easily calculated from standard lipid profile. As a marker of lipoprotein particle size it adds predictive value beyond that of the individual lipids, and/or TC/HDL-C ratio.

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.

Fractional esterification rate of HDL particles in patients with type 2 diabetes. Relation to coronary heart disease risk factors.

OBJECTIVE: To study the fractional esterification rate of cholesterol on HDL particles (FERHDL) in adults with type 2 diabetes and assess its correlation with serum lipids and other coronary heart disease (CHD) risk factors. RESEARCH DESIGN AND METHODS: FERHDL was measured in 90 adult (57 men, 33 women) patients by an isotopic assay method involving several steps, including preparation of VLDL- and LDL-depleted plasma, labeling of the sample with a trace amount of tritiated cholesterol, separation of free and esterified cholesterol fractions by chromatography post incubation, and subsequent counting of radioactivity in the individual fractions. RESULTS: Male patients have higher FERHDL values than their female counterparts. When HDL cholesterol was controlled for in a multivariate regression analysis, the sex factor was not significant. There was a significant positive correlation between FERHDL and plasma total cholesterol (r = 0.32), triglycerides (r = 0.82), apolipoprotein B (apo B; r = 0.48), insulin (r = 0.46), BMI (r = 0.31), and waist-to-hip ratio (WHR; r = 0.50). There was a negative correlation between FERHDL and HDL cholesterol (r = -0.76) and apolipoprotein AI (r = -0.60). When both HDL cholesterol and triglycerides were controlled for, the only significant correlation was between FERHDL and BMI. CONCLUSIONS: Non-insulin-requiring type 2 diabetic patients have FERHDL, which correlated positively with triglycerides and negatively with HDL cholesterol. The positive correlation of FERHDL with serum insulin, WHR, total cholesterol, and apo B, but not that with BMI, loses its significance when HDL cholesterol and triglycerides are controlled. The sex difference between men and women in FERHDL also loses its significance when HDL cholesterol is controlled.

Effect of the phospholipid vehicle on the transport of cholesterol in rats.

Rats were injected intravenously with liposomes made of [4(-14)C] cholesterol with [32P]lysolecithin, or [4(-14)C]cholesterol with [32P]lecithin. The clearance of both radioactive labels from plasma was observed, as well as their distribution in the organs after 15 and 60 min. At the same time, the esterification of injected [14C]cholesterol and the conversion of [32P]lysolecithin to [32P]lecithin and vice versa were examined. [14C]Cholesterol administered with lysolecithin was cleared from the plasma at a higher rate than with lecithin. Consequently the radioactivity of [14C]cholesterol in the aorta, heart, lung, kidney and liver changed with the applied phospholipid; with lysolecithin it was higher than with lecithin. Lysolecithin itself was distributed among the organs more evenly than lecithin, which accumulated most in the liver. If administered with lysolecithin, [14C]cholesterol was esterified in the plasma in a significantly higher proportion than if administered with lecithin. The antiatherogenous effect of lecithin and the atherogenous effect of lysolecithin are considered on the basis of different transport properties of these phospholipids.

Rate of LCAT-mediated cholesterol esterification and serum lipids during etiroxate therapy in hyperlipoproteinemia.

Changes in the rate of the plasma cholesterol ester production mediated by lecithin: cholesterol acyltransferase (LCAT, E.C. 2.3.1.43) were examined in 15 patients suffering from types II and IV HLP who had been treated for 14 weeks with etiroxate. Whereas the plasma cholesterol concentration decreased significantly only in the initial phase of the therapy, the rate of cholesterol esterification increased gradually and attained at the end of the study a value exceeding by 50% the initial level. The final fractional turnover rate nearly equalled that characteristic for the control group of healthy subjects, in spite of the fact that the concentration of plasma cholesterol in the diseased subjects was higher by 50-100%. Triglyceride concentration decreased only transitorily in the course of the therapy with etiroxate. It is concluded that etiroxate is likely to normalize the rate of cholesterol turnover in the endogenous pool.

Lysolecithin-dependent release of cholesterol from rat plasma.

We studied the effect of lysolecithin on the clearing of plasma cholesterol. The immediate and maximal conversion of plasma lecithin to lysolecithin was produced in rats by intravenous injection of phospholipase A. The changes which took place in the converted lysolecithin and of cholesterol were followed in rats which had previously received [32-P]phosphate and [14-C]cholesterol. We followed simultaneously the in vitro changes in blood removed immediately after the in vivo administration of phospholipase A. The experiments showed that a substantial part of the plasma lecithin was converted to lysolecithin within the first minute after intravenous administration of phospholipase A. In the course of 60 min of blood incubation, the ratio of plasmatic lysolecithin in the closed system continued to increase. At the same time the content of cholesterol also increased. In vivo, the converted lysolecithin was quickly released from the plasma, so that within 10 min the original lecithin content dropped to 15-5% depending on the dose of phospholipase A that had been administered. The content of sphingomyelin and lysolecithin, which increased only temporarily shortly after injection, did not alter during the experiment. The level of plasma cholesterol esters, however, dropped significantly, whereas the free cholesterol content increased. The molar ratio of the drop in lipid phosphorus and cholesterol esters in plasma after the administration of phospholipase A was similar. A significantly higher cholesterol content was found in the liver of animals treated with phospholipase A.

The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)).

OBJECTIVES: To evaluate if logarithm of the ratio of plasma concentration of triglycerides to HDL-cholesterol (Log[TG/HDL-C]) correlates with cholesterol esterification rates in apoB-lipoprotein-depleted plasma (FER(HDL)) and lipoprotein particle size. DESIGN AND METHODS: We analyzed previous data dealing with the parameters related to the FER(HDL) (an indirect measure of lipoprotein particle size). In a total of 1433 subjects from 35 cohorts with various risk of atherosclerosis (cord plasma, children, healthy men and women, pre- and postmenopausal women, patients with hypertension, type 2 diabetes, dyslipidemia and patients with positive or negative angiography findings) were studied. RESULTS: The analysis revealed a strong positive correlation (r = 0.803) between FER(HDL) and Log(TG/HDL-C). This parameter, which we propose to call "atherogenic index of plasma" (AIP) directly related to the risk of atherosclerosis in the above cohorts. We also confirmed in a cohort of 35 normal subjects a significant inverse correlation of LDL size with FER(HDL) (r = -0.818) and AIP (r = -0.776). CONCLUSION: Values of AIP correspond closely to those of FER(HDL) and to lipoprotein particle size and thus could be used as a marker of plasma atherogenicity.

Advances in understanding of the role of lecithin cholesterol acyltransferase (LCAT) in cholesterol transport.

We review the structure and function of lecithin cholesterol acyl transferase (LCAT), the advances in the studies of molecular genetics of LCAT and its deficiency states as well as the developments in assessment of LCAT activity particularly the concept of measurement of fractional esterification rate of plasma cholesterol in the absence of apoB lipoproteins (FER(HDL)) as an indication of atherogenic risk. We discuss LCAT reaction from two points of view: one that is consistent with the general belief in LCAT antiatherogenic potential and another, namely, a proposed concept of potentially opposing roles of LCAT in normal and dyslipidemic plasmas. While other plasma lipoproteins can (in addition to HDL) provide unesterified cholesterol (UC) for LCAT reaction, HDL may play an unique role in trafficking of newly formed cholesteryl esters (CE) rather than as a primary acceptor of cellular cholesterol. Thus, the plasma HDL, specifically the larger (HDL2b) particles, direct the efflux of most of (LCAT produced) CE to its specific catabolic sites rather than to potentially atherogenic VLDLs and back to LDLs.

Effect of ciprofibrate on lipoprotien metabolism and oxidative stress parameters in patients with type 2 diabetes mellitus and atherogenic lipoprotein phenotype.

The effect of ciprofibrate therapy on plasma lipids and lipoproteins, HDL and LDL subfraction profile, fractional esterification rate of HDL cholesterol (FER(HDL)) and the resistance of LDL and serum lipids to oxidation was studied in 24 males with type 2 diabetes and atherogenic lipoprotein phenotype (ALP). We also examined the effect of ciprofibrate therapy on oxidative DNA damage in peripheral lymphocytes. No differences in glucose, HbA1C and BMI levels were found after three months of ciprofibrate therapy. Ciprofibrate significantly decreased total cholesterol and triglyceride levels by 5.5% and 50% (p = 0.05; 0.001, respectively) and increased HDL-cholesterol levels by 8.5% (p = 0.05). FER(HDL) and LDL subfraction profile were also favorably affected. However, no effect on HDL subclasses was found. There were no statistically significant differences in lipid resistance to oxidation measured in serum and in LDL (lag time and Vmax) before and after therapy. No significant effect of ciprofibrate was found on oxidative DNA damage. The evaluation of the relationship between oxidative damage of purines with lag time in LDL and maximal rate of serum lipid oxidation showed significant correlations after therapy (r = -0.58; 0.47, p = 0.01; 0.05, respectively), but only trends before starting ciprofibrate treatment. Type 2 diabetes mellitus represents a complex metabolic disorder expressed in glucose and lipoprotein disturbances and increased oxidative stress. Ciprofibrate therapy favorably affected major features of lipid abnormalities of diabetic patients, but the level of oxidative stress assessed by in vitro and in vivo methods was not changed. The evaluation of expected logical correlations between the parameters of lipoprotein metabolism, lipid resistance in serum and LDL, and oxidative DNA damage showed that those correlations were more relevant and significant after ciprofibrate treatment and were not related with glucose homeostasis.

Lecithin cholesterol acyltransferase and possible origin of lysolecithin in rabbit aqueous after a damage of blood-aqueous barrier.

Rabbit eye aqueous humor contains lysolecithin (LPC); the LPC concentration markedly increases, if the integrity of the hemato-aqueous barrier is impaired. It is assumed that LPC plays a causal role in the development of cataract because of its detergent action. We have studied the mechanism of LPC cumulation in the aqueous after a mechanical, endotoxic or immunological damage to the hemato-aqueous barrier. We measured in aqueous samples the activity of lecithin cholesterol acyltransferase (LCAT, EC 2.3.1.43), an enzyme which produces LPC and cholesteryl esters in the plasma. The transfer of phospholipids from the plasma into the aqueous was examined in vivo in 32p-prelabeled rabbits. Whereas LCAT was absent in the aqueous humor of intact eyes, an increased transesterification activity could be detected in all cases of impaired hemato-aqueous barrier. The proportion of LPC in aqueous phospholipids was similar to that found in high density lipoproteins, whereas whole plasma and low density lipoproteins contained a much lower proportion of LPC. An increased plasma level of LPC induced by the treatment of rabbits with phospholipase A2 in vivo, did not by itself lead to a preferential passage of plasma LPC through the blood-aqueous barrier. The experimental results rather imply that an impaired blood-aqueous barrier permitted an enhanced transfer from the plasma of intact HDL carrying also LPC and LCAT, and that the enzyme subsequently produced increased amounts of LPC in situ.

Uptake of cerebroside, cholesterol and lecithin by brain myelin and mitochondria.

The uptake of emulsified labeled lipids by rat brain myelin and mitochondria was studied. Cerebroside and lecithin uptakes were greatly stimulated by addition of salts, particularly those containing divalent cations. Cholesterol uptake was not influenced by salts. Increasing concentrations of detergent (non-ionic) were inhibitory. Delipidated membranes took up much less lipid, but pretreatment with lecithin partially restored the ability to take up cerebroside and cholesterol. The lipid uptake appears to be nonenzymatic and appears to depend on the size of the emulsified particles. The possible role of such a phenomenon in membrane formation and maintenance is discussed.

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.

Measurement of fractional esterification rate of cholesterol in plasma depleted of apoprotein B containing lipoprotein: methods and normal values.

The distribution of differently sized HDL particles in the plasma can be assessed by measurement of the fractional rate of cholesterol esterification (FERHDL). We have characterized the isotopic assay and compared it to the enzymatic measurement of the decrease in HDL free cholesterol (mass assay). The normal values of FERHDL were established in 116 apparently healthy individuals. The isotopic assay is particularly sensitive to changes in the incubation temperature above 37 degrees C. The reproducibility of the assay in aliquots of plasma stored at -20 degrees C and -70 degrees C for 3 months and even up to 2 years was high. Intraindividual variability of FERHDL is low. In the subjects in whom FERHDL was measured over a 3-month and 2-5 years' period, FERHDL showed a low variability (97.5 +/- 2.6% and 101 +/- 6.0% respectively in a paired t-test). Comparison of the isotopic assay and the mass assay revealed that the isotopic assay was much more reproducible. Normal values of FERHDL and the HDL subspecies distribution (using gradient gel electrophoresis) were established in 63 men and 56 women. The average values of FERHDL were significantly higher in men (16.8 +/- 4.5%/h) than in women (10.6 +/- 3.6%/h) and correlated well with the distribution of the HDL subspecies. FERHDL radioassay as a highly reproducible method for the assessment of HDL subspecies distribution which may be suitable for both retrospective and prospective studies of diseases of atherogenous origin.

Gender differences in plasma levels of lipoprotein (a) in patients with angiographically proven coronary artery disease.

The objective of the study was to assess the association between plasma levels of lipoprotein(a) [Lp(a)] and the presence of angiographically defined coronary artery disease (aCAD). Patients (346 men and 184 women) undergoing selective coronary angiography (SCA) were classified into groups with positive [aCAD(+)] and negative [aCAD(-)] findings and their age, body mass index (BMI), waist circumference, blood pressure, smoking, plasma total, LDL-, HDL-cholesterol (TC, LDL-C, HDL-C), triglycerides (TG), apolipoprotein B (apoB), Log(TG/HDL-C) and TC/HDL-C were determined. Concentration of plasma Lp(a) was estimated using the commercial solid phase two-side immunoradiometric assay of apolipoprotein apo(a). The plasma Lp(a) was significantly higher in both women and men with aCAD(+) compared to those with aCAD(-). While there was no significant difference in the Lp(a) level between men and women with aCAD(-) (median 138 vs. 145 units/l), the women with aCAD(+) had almost twice as high Lp(a) levels as men (median 442 vs. 274 units/l, p<0.001). Women with aCAD(+) had also significantly lower HDL cholesterol levels (1.09 vs. 1.20 mmol/l, p<0.05), higher triglycerides (1.82 vs. 1.46 mmol/l, p<0.05) and Log(TG/HDL-C) than women with aCAD(-). The differences in Lp(a) between positive and negative findings remained highly significant (p<0.001 in women, p<0.05 in men) after the adjustment for age, plasma HDL- and LDL-cholesterol and triglycerides in logistic regression analyses. In logistic regression model the Lp(a) and Log(TG/HDL-C) and smoking in women but smoking and age in men were the most powerful predictors of positive aCAD findings. Our findings suggest that Lp(a) is more strongly associated with aCAD+ in women than in men.

Developmental aspects of lipid metabolism.

It was confirmed that the main source of energy for growth and development in the neonatal period was fat. Considerable attention was paid to the development of both white adipose tissue (WAT) and brown adipose tissue (BAT) in the rat and human newborn. Cholesterol metabolism during development was studied in the liver, the small intestine and both WAT and BAT. Brown adipose tissue of rats and adipose tissue from human newborns require carnitine for optimum respiration and fatty acid oxidation. Surprisingly, carnitine enhanced lipolysis in human newborn adipose tissue, intravenously-fed newborn patients exhibited a rapid decrease of plasma level of carnitine and its esters, indicating a greater requirement for exogenous carnitine than in adult subjects (52 references).

Development of gastrointestinal functions.

Data are summarized about digestion and absorption of carbohydrates, lipids and proteins during mammalian perinatal development including human fetuses. Corresponding with the high fat intake in suckling rats, absorption of triglycerides was found to be approximately 2-3 times higher in suckling than in adult rats. Carnitine contents of the small intestinal mucosa of rats decrease postnatally, reaching adult levels at the time of weaning. Other studies suggested that gluconeogenesis may occur in the small intestine in the neonatal period. The intestinal mucosa of infant rats produces ketones; it was suggested that ketone production is to a large extent due to a breakdown of long-chain fatty acids. Studies dealing with the development of colonic sodium transport in rats are described. Other studies on the developing colon showed that the proximal colon resembles ileum during the early postnatal period. Developmental changes of the "specialization" of intestinal segments are reviewed. In all studies attention is given to the maturative effects of hormones of the adrenal cortex and thyroid gland (88 references).

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).

Lecithin:cholesterol acyltransferase as a possible diagnostic tool in ischemic heart disease.

Basal values of lecithin:cholesterol acyltransferase (LCAT) were estimated in healthy subjects, in patients with the so-called risk ischemic heart diseases (IHD)--obesity, diabetes, hypertension, and hyperlipoproteinemia II--and in patients with a IHD-infarction of the myocardium. A precise method employing a 14C-4-cholesterol-labeled common normolipidemic substrate was used. A highly significant difference in the average values of LCAT activity between healthy men and women was found. LCAT in men with 'risk' diseases decreased, while in women it remained at the level of the reference group. To assess the dependence between LCAT-dependent indicators and IHD, criteria for evaluating the deviations from reference values were proposed. The number of deviations from the reference group increased in the sequence: obesity, hypertension, diabetes, hyperlipoproteinemia, and the infarction of the myocardium.

Defect in cholesterol esterification associated with renal diseases.

Changes in lipidaemia and in cholesterol esterification rate were investigated in 65 patients with chronic mesangial glomerulonephritis (GN), and in 26 patients with polycystic kidneys (PL), as well as in age- and sex-matched control groups. As compared to the controls, a slightly significant increase in cholesterol and triglyceride concentrations was found only for the GN group, whereas the rate of cholesterol esterification showed a highly significant reduction in both groups of diseased subjects. The average values of molar esterification rate (MER) were, respectively, 75.4 and 61.6 mumol . l-1 . h-1 for the GN and PL groups, the respective control values being 96.9 and 91.1. Fractional esterification rate (FER) reflecting the rate of cholesterol exchange between blood and tissues fell in the same two groups of patients to 4.38 and 4.40% . h-1, respectively (controls 6.93 and 6.17). Both the changes in cholesterol esterification rates and a relative increase in the ratio of unesterified to esterified cholesterol were found in patients with low as well as normal glomerular filtration rates.