BACKGROUND

The information about the effect of fried-oily fish consumption on cholesterol metabolism is rather scarce.

OBJECTIVE

To test the effect of olive oil-fried sardine consumption on cholesterol content in the serum, lipoproteins, spleen and adipose tissue of hypercholesterolemic rats.

METHODS

Hypercholesterolemia was induced for 3 weeks by a casein + olive diet containing cholesterol and bovine bile (COC). Rats were later switched for 2 weeks to diets containing casein + olive oil (CO), olive oil-fried sardines (S), and olive oil-fried sardines-cholesterol-bovine bile (SC) while one rat group continued on the COC diet. Cholesterol was determined in serum, lipoproteins, adipose tissue and spleen.

RESULTS

The SC diet markedly blocked the hypercholesterolemic induction of the cholesterol-raising agents. Dietary cholesterol withdrawal decreased serum cholesterol levels, with the S diet inducing the highest decrease in serum and VLDL + LDL-cholesterol levels. Cholesterol withdrawal decreased spleen total cholesterol content and weight but the S diet was unable to reduce spleen cholesterol content (micromol/g) more than CO diet. Adipose tissue of S rats displayed the lowest cholesterol values. Cholesterol (mmol/g) of adipose tissue correlated very significantly with total serum cholesterol (r = 0.9225, p < 0.0001) and VLDL + LDL-cholesterol (r = 0.9313, p < 0.0001).

CONCLUSIONS

Cholesterol in adipose tissue was very sensitive to variations in plasma cholesterol. Consumption of fried sardines interacts with cholesterol withdrawal, accelerating serum cholesterol normalization and reduction of cholesterol levels in adipose tissue.

It is known that plasma low density lipoproteins (LDL) contain a great amount of vitamin E and that LDL enter cells via the specific receptor-mediated mechanism. In this study, we aimed to investigate the transport of alpha-tocopherol from plasma to tissues in subjects with non-insulin-dependent diabetes mellitus (NIDDM) with poor glycaemic control; and the relationships between alpha-tocopherol and plasma lipid and lipoprotein levels. alpha-Tocopherol determination was carried out by colorimetric assay according to the modified micromethod of Fabianek et al. The mean plasma alpha-tocopherol and (LDL + VLDL)-alpha-tocopherol levels increased significantly in the diabetic group as compared to control (P less than 0.05 and P less than 0.02), whereas the high density lipoprotein (HDL)-alpha-tocopherol level was significantly lower in the diabetic group than that in the controls (P less than 0.05). Correlations between plasma alpha-tocopherol levels showed close positive relationships (r = 0.87, r = 0.75 and r = 0.78, respectively, P less than 0.001). A strong positive correlation was also observed between alpha-tocopherol and the cholesterol content, either in the HDL or in the (LDL + VLDL) fractions (r = 0.75 and r = 0.77; P less than 0.001). These findings indicate that there is a direct positive relationship between lipid and alpha-tocopherol concentrations. The increased level of alpha-tocopherol in the LDL + VLDL fraction and decreased level in HDL in these patients could be attributed to the impairment of the cholesterol uptake of the cells by the receptor mediated mechanism.

OBJECTIVE

To examine the association between the kinetics of very-low-density-lipoprotein (VLDL)-apolipoprotein B-100 (apoB) and intraperitoneal, retroperitoneal, subcutaneous abdominal, and total adipose tissue masses (IPATM, RPATM, SAATM, and TATM, respectively) in overweight/obese men.

METHODS

Hepatic secretion of VLDL was measured using an intravenous infusion of 1-[(13)C]-leucine in 51 men with a wide range of body mass index (25.1 to 42.2 kg/m(2)). Isotopic enrichment of VLDL-apoB was measured using gas chromatography-mass spectrometry and a multicompartmental model used to estimate VLDL-apoB metabolic parameters. IPATM, RPATM, and SAATM (kilograms) were quantified between T11 and S1 using magnetic resonance imaging; TATM (kilograms) was determined using bioelectrical impedance. Insulin resistance was estimated by homeostasis model assessment (HOMA) score.

RESULTS

In stepwise regression, IPATM was the best predictor of hepatic secretion of VLDL-apoB (r = 0.390, p < 0.005) and TATM was the best predictor of VLDL-apoB fractional catabolic rate (r = 0.282, p < 0.05). IPATM remained significantly associated with VLDL-apoB secretion after adjusting for TATM or HOMA score (r = 0.360, p < 0.01 and r = 0.310, p < 0.05, respectively). This association was also independent of age, dietary intake, and body mass index. None of the fat compartments were significantly associated with the fractional catabolic rate of VLDL-apoB after adjusting for HOMA score.

CONCLUSIONS

In overweight/obese men, the quantity of both IPATM and TATM determine the kinetics of VLDL-apoB. The effect of IPATM on VLDL-apoB secretion is independent of both total fat mass and the degree of insulin resistance.

We have characterized and quantified the two major plasma apoproteins of high density lipoproteins (HDL), apolipoproteins A-I (apoA-I) and E (apoE), of guinea pigs fed standard chow (normal) or chow supplemented with 1% cholesterol (cholesterol-fed). ApoA-I isolated from plasma HDL of the normal guinea pig exists in six polymorphic forms (pI 5.75-5.40). A similar isoform pattern of this apoprotein was present in nascent HDL isolated from perfused livers of normal and cholesterol-fed animals. This apoprotein contains cysteine and isoleucine and is slightly different in overall amino acid composition from apoA-I of human and rat, but activates lecithin:cholesterol acyltransferase from human plasma with an activation curve almost identical to that obtained with human apoA-I. ApoE present in nascent VLDL and HDL from perfused liver of normal animals contains three isoforms (pI 5.42-5.34). Following cholesterol feeding, the numbers of apoE isoforms from perfused livers were increased from three to five or more by shifting the major component (pI 5.42) to more acidic isoforms (pI 5.28-5.17). This shifting was mostly reversible when apoE was treated with neuraminidase, suggesting that cholesterol feeding leads to a modification of apoE by increasing its content of sialic acid. Similar changes of apoE isoforms were also observed in plasma lipoproteins as early as 10 days after cholesterol feeding. The amino acid compositions of four apoE isoform fractions isolated from plasma HDL of cholesterol-fed guinea pigs were similar to that of parent apoE. The plasma concentrations of apoA-I and apoE, measured by electroimmunoassay, were 6.2 +/- 2.0 and 2.2 +/- 0.5 mg/dl, respectively, in guinea pigs fed standard chow. In animals that had been fed 1% cholesterol, plasma levels of apoA-I slightly increased in 1 week and showed a twofold increase in 8-10 weeks. Plasma levels of apoE, on the other hand, sharply increased by 10-fold in 1 week and up to 22-fold in 8-10 weeks on the cholesterol diet.-Guo, L. S. S., R. L. Hamilton, J. P. Kane, C. J. Fielding, and G. C. Chen. Characterization and quantitation of apolipoproteins A-I and E of normal and cholesterol-fed guinea pigs.

The plasma membrane receptor for VLDL and vitellogenin from oocytes of Japanese quail (Coturnix coturnix japonica) was characterized and compared with that of another domestic fowl, the chicken (Gallus domesticus). When visualized by ligand blotting with biotinylated or 125I-labeled lipoproteins, the quail VLDL/vitellogenin receptor had an apparent M(r) of 95 kDa under nonreducing conditions, identical to that of the chicken receptor. Upon analysis by ligand blotting, binding of radiolabeled quail plasma VLDL to the quail oocyte receptor seemed to be saturable and exhibited high affinity (apparent Kd of 13.9 mg/L). Cross-reactivity, at the level of ligand recognition, was observed between quail and chicken VLDL/vitellogenin receptors, and immunological relatedness was demonstrated by Western blotting with a rabbit anti-chicken oocyte VLDL receptor antibody. In contrast, a species difference was observed in the apolipoprotein VLDL-II moiety of plasma VLDL. Chicken apolipoprotein VLDL-II, an 82-amino acid protein with a disulfide crosslink at residue 75 (the sole cysteine residue), existed as a homodimer of 9.5 kDa subunits and, to a lesser extent, as a monomer. Quail apolipoprotein VLDL-II existed only in monomeric form without reduction and lacked cysteine. The present results demonstrate that, despite a difference in an apolipoprotein moiety of VLDL, quail and chicken oocyte lipoprotein receptors share key structural and functional elements. This lends further support to the notion that receptor recognition is mediated by the common VLDL component, apolipoprotein B.

The effects of orally supplemented dl -alpha-tocopherol on the plasma concentration of lipid-soluble antioxidants and their distribution in very-low-density, low-density and high-density lipoproteins (VLDL, LDL and HDL) was investigated in a cohort of control normocholesterolemic adult subjects receiving 600 mg alpha-tocopherol daily for 2 weeks. This regimen did not modify the plasma lipid profile (total, LDL and HDL cholesterol and triglycerides) and chemical composition of VLDL, LDL and HDL. Plasma concentration of alpha-tocopherol increased from 19.44+/-4.77 to 38.03+/-9.06 µm and this was associated with slight decrease in the concentration of gamma-tocopherol from 1.27+/-0.97 to 0.99+/-1.17 µm, without any significant changes of either lycopene and beta-carotene. Qualitatively similar changes were found in VLDL, LDL and HDL but the net increase of alpha-tocopherol in plasma did not correlate with the increase in alpha-tocopherol content in any of the lipoprotein types. Following supplementation, the percentage of total plasma alpha-tocopherol pool carried by VLDL increased from 20.97+/-6.07% to 33.57+/-6.97%, whereas it decreased from 41.85+/-7.02% to 36.36+/-5.69% in the case of LDL and from 37.17+/-6.04% to 30.05+/-4.88% in the case of HDL. The absolute and relative enrichment of alpha-tocopherol in either VLDL and LDL did not exhibit any statistically relevant correlation with the chemical composition of these lipoproteins in the different subjects investigated. On the other hand, the amount of alpha-tocopherol enriching the HDL particles was inversely related to the relative abundance of protein (r =0.449;P<0.05) and directly to the phospholipid/protein ratio (r =0.480, P<0.05). 2000 Academic Press@p$hr Copyright 2000 Academic Press.

OBJECTIVE

The objective of the study was to examine the effect of lipoprotein-associated cyclosporine on hepatic metabolism, hepatic lipoprotein receptors, and renal toxicity in comparison to the current commercially available cyclosporine (CSA) product.

METHODS

Rats within the same group were given one of the following treatments: 10 mg/kg of CSA, plasma-CSA, very low-density lipoprotein (VLDL)-CSA, low-density lipoprotein (LDL)-CSA, LDL, high-density lipoprotein (HDL)-CSA, 1 mL/kg of vehicle, or saline intravenously for 14 days. Urine and blood samples were evaluated for renal function. Hepatic microsomes were prepared for immunoblotting and in vitro catalytic assays of CYP activity. Reverse transcription polymerase chain reaction (RT-PCR) was used to examine genetic regulation.

RESULTS

(1) There were no statistical differences in cholesterol levels in lipoprotein-associated CSA groups as compared with vehicle controls. (2) A significant decrease in creatinine clearance was seen in the plasma-CSA treated group (56%; P < 0.05). (3) No suppressions of CYP3A protein, activity or mRNA were found in the VLDL-CSA treated group. (4) CYP3A mRNA was suppressed to a greater degree in the LDL- and HDL-CSA treated groups as compared with the suppression caused by CSA alone. (5) A significant suppression of hepatic low-density lipoprotein receptor (LDL-R) mRNA levels was found in the LDL-CSA (50%; P = 0.0333) and plasma-CSA (40%; P = 0.1138), which was not attributed to LDL alone. (6) Significant suppression of scavenger-receptors class B type I (SR-BI) mRNA levels was found in the plasma-CSA group, although no significant differences in SRBI protein levels were seen between groups.

CONCLUSIONS

Specific lipoprotein-CSA complexes appear to alter metabolic responses differently in comparison to CSA alone, indicating that the metabolism of CSA is dependent on the in vivo disposition of lipoprotein-CSA. Furthermore, LDL-R is one regulatory factor responsible for altering CSA metabolism as a result of an increase in uptake of CSA into hepatocytes.

<Abst<em>r</em>actText>Fenofib<em>r</em>ate, a pe<em>r</em>oxisome p<em>r</em>olife<em>r</em>ato<em>r</em>-activated <em>r</em>ecepto<em>r</em>-α (PPARα) agonist, is used to t<em>r</em>eat patients with hype<em>r</em>choleste<em>r</em>olemia and hype<em>r</em>t<em>r</em>iglyce<em>r</em>idemia in o<em>r</em>de<em>r</em> to <em>r</em>educe the <em>r</em>isk of development of the athe<em>r</em>oscle<em>r</em>otic ca<em>r</em>diovascula<em>r</em> disease. Howeve<em>r</em>, it exe<em>r</em>ts pleiot<em>r</em>opic effects beyond co<em>r</em><em>r</em>ecting athe<em>r</em>ogenic dyslipidemia to t<em>r</em>eat hype<em>r</em>choleste<em>r</em>olemia.</Abst<em>r</em>actText><Abst<em>r</em>actText>The aim of this study was to investigate the potential effects of fenofib<em>r</em>ate on endothelial function by analyzing the se<em>r</em>um nit<em>r</em>ic oxide (NO) levels in patients with hype<em>r</em>t<em>r</em>iglyce<em>r</em>idemia.</Abst<em>r</em>actText><Abst<em>r</em>actText>Lipid p<em>r</em>ofiles and se<em>r</em>um NO levels we<em>r</em>e assessed in 56 healthy adults aged 29 to 84 yea<em>r</em>s, befo<em>r</em>e and afte<em>r</em> 12 weeks of fenofib<em>r</em>ate (250 mg/d; n = 30) o<em>r</em> placebo (n = 26). App<em>r</em>op<em>r</em>iate dieta<em>r</em>y suggestions fo<em>r</em> hype<em>r</em>t<em>r</em>iglyce<em>r</em>idemia we<em>r</em>e made fo<em>r</em> all patients. This study was <em>r</em>andomized, double-blind and placebo-cont<em>r</em>olled in design.</Abst<em>r</em>actText><Abst<em>r</em>actText>Total choleste<em>r</em>ol, low-density lipop<em>r</em>otein (LDL), ve<em>r</em>y low-density lipop<em>r</em>otein (<em>VLDL</em>) and t<em>r</em>iglyce<em>r</em>ide levels significantly dec<em>r</em>eased; high-density lipop<em>r</em>otein (HDL) and NO levels significantly inc<em>r</em>eased afte<em>r</em> 12 weeks of fenofib<em>r</em>ate the<em>r</em>apy. We obse<em>r</em>ved a statistically significant co<em>r</em><em>r</em>elation between the inc<em>r</em>ease in se<em>r</em>um NO levels and dec<em>r</em>ease in se<em>r</em>um t<em>r</em>iglyce<em>r</em>ide levels (<em>r</em> = -0.42, p = 0.02) in the fenofib<em>r</em>ate g<em>r</em>oup.</Abst<em>r</em>actText><Abst<em>r</em>actText>The positive effect of sho<em>r</em>t-te<em>r</em>m fenofib<em>r</em>ate t<em>r</em>eatments on vascula<em>r</em> endothelial functions in patients with hype<em>r</em>t<em>r</em>iglyce<em>r</em>idemia has been demonst<em>r</em>ated by inc<em>r</em>easing the se<em>r</em>um NO levels. Agents such as fenofib<em>r</em>ate ta<em>r</em>geting PPARα-associated signaling pathways show p<em>r</em>omise as an alte<em>r</em>native t<em>r</em>eatment of vascula<em>r</em> dysfunction <em>r</em>elated to advanced age and hype<em>r</em>lipidemia.</Abst<em>r</em>actText>

The purpose of this study was to examine the influence of the physical activity level of men and women on the very-low-density lipoprotein (VLDL) subfractions and lipoprotein(a) [Lp(a)]. Fifty-four men (n = 30) and women (n = 24) aged 30 to 53 years were recruited based on their level of activity over the past 2 years, and formed three groups: sedentary (S), no routine activity; recreational exercise (R), routine moderate exercise three to five times per week; and trained (T), competition-based, high-volume aerobic training five to seven times per week. Each subject underwent a maximal oxygen consumption (VO2max) test and was measured for body composition (skinfolds) and waist to hip ratio (WHR). Following a prescribed 24-hour diet and abstinence from activity, a blood sample was obtained from each subject and the plasma was analyzed for cholesterol and triglycerides (TGs) in VLDLVLDLVLDLVLDL-C was higher in men than in women, but no gender differences were observed in VLDL subfractions. VLDLVLDLR and T, even though total VLDL-TG, LDL-C, and HDL-C values were not different among the groups. Values for Lp(a) were not significantly different between men and women or among the groups. The two exercising groups were not different on any lipoprotein variable or WHR. VLDLVLDL subfraction pattern and WHR, but not Lp(a). In addition, long-term recreational activity is associated with a lipoprotein profile and WHR similar to those obtained with higher-volume exercise training.

OBJECTIVE

To evaluate the effect of chronic consumption of di- and triheptanoin on hepatic steatosis (HS) in rats.

METHODS

Wistar rats were submitted to a diet AIN-93 with 0, 30 or 50% of its oil substituted with an oil rich in di- and triheptanoin, groups TAGC(7)0, TAGC(7)30 and TAGC(7)50 respectively, for nine months. The control group received Labina(R). Liver histology, hepatic lesion and function proofs, glycemia and lipid profile, were performed. Variance analyses, F-test, Dunnet s test and uni- and multivariate regression analyses were performed (p<0.05).

RESULTS

TAGC(7)0, TAGC(7)30 and TAGC(7)50 developed HS; 80% of severe cases in TAGC(7)0, as against 40% in TAGC(7)50. The absolute (ALW) and relative (RLW) liver weights were higher in TAGC(7)0 and TAGC(7)30, and glycemia was greater in TAGC(7)30 and TAGC(7)50, than in the Control. Total cholesterol, LDL-c, LDL-c/HDL-c and total proteins were higher in the Control. The experimental oil reduced RLW and showed a tendency in the reduction of body weight, ALW, percentage of hepatic lipids and the severity of HS. The explanatory variables in relation to HS were final weight, glycemia, albumin, HDL-c, LDL-c, LDL-c/HDL-c, VLDL-c and alkaline phosphatase.

CONCLUSIONS

It is suggested that di- and triheptanoin have a hepatoprotector effect against HS, in rats, in a dose-dependent manner.

OBJECTIVE

To investigate lipid metabolism and the relationship with monocyte expression of the fatty acid translocase CD36 in South Asians.

METHODS

An observational study of South Asians whom as an ethnic group have - a higher risk of developing diabetes. The susceptibility to diabetes is coupled with an earlier and more rapid progression of micro-, and macro-vascular complications. Twenty-nine healthy South Asian participants [mean age 34.6 (8.9) years, 76.2% male, mean body-mass index 25.0 (5.2) kg/m(2)] were recruited from an urban residential area of central Birmingham (United Kingdom). The main outcomes measured were post prandial (30 min) and post absorptive (120 min) changes from fasting (0 min) in circulating lipoproteins, lipds and hormones, and monocyte expression of CD36 post injection of a 75 g oral glucose challenge. The inducements of variations of monocyte CD36 expression were analysed.

RESULTS

Our results showed evident changes in monocyte CD36 expression following the glucose challenge (P < 0.001). Non-esterified fatty acids (NEFA) levels decreased progressively during the challenge (P < 0.001), in contrast to increased cholesterol (but not triglyceride) concentrations within very low density lipoprotein (VLDL) and low density lipoprotein subfractions (P < 0.01). Levels of, glucose, serum triglycerides and high density lipoprotein cholesterol remained largely unchanged. Variations of monocyte CD36 were negatively (r = -0.47, P = 0.04) associated to fat from the diet and positively to carbohydrate from the diet (r = 0.65, P < 0.001).

CONCLUSIONS

These data suggest that the initiation of VLDL genesis follows the consumption of glucose within this population, inferring that the sequestration of NEFA from these particles happens due to the increased availability of CD36 receptors. While these are preliminary results, it would appear that lifestyle exposures have a role in moderating the expression of CD36.

<Abst<em>r</em>actText>Obse<em>r</em>vational studies often infe<em>r</em> hepatic de novo lipogenesis (DNL) by measu<em>r</em>ing ci<em>r</em>culating fatty acid (FA) ma<em>r</em>ke<em>r</em>s; howeve<em>r</em>, it <em>r</em>emains to be elucidated whethe<em>r</em> these ma<em>r</em>ke<em>r</em>s accu<em>r</em>ately <em>r</em>eflect hepatic DNL.</Abst<em>r</em>actText><Abst<em>r</em>actText>We investigated associations between fasting hepatic DNL and p<em>r</em>oposed FA ma<em>r</em>ke<em>r</em>s of DNL in subjects consuming thei<em>r</em> habitual diet.</Abst<em>r</em>actText><Abst<em>r</em>actText>Fasting hepatic DNL was assessed using 2H2O (deute<em>r</em>ated wate<em>r</em>) in 149 nondiabetic men and women and measu<em>r</em>ing the synthesis of ve<em>r</em>y low-density lipop<em>r</em>otein t<em>r</em>iglyce<em>r</em>ide (<em>VLDL</em>-TG) palmitate. FA ma<em>r</em>ke<em>r</em>s of blood lipid f<em>r</em>actions we<em>r</em>e dete<em>r</em>mined by gas ch<em>r</em>omatog<em>r</em>aphy.</Abst<em>r</em>actText><Abst<em>r</em>actText>Neithe<em>r</em> the lipogenic index (16:0/18:2n-6) no<em>r</em> the SCD index (16:1n-7/16:0) in <em>VLDL</em>-TG was associated with isotopically assessed DNL (<em>r</em> = 0.13, P = 0.1 and <em>r</em> = -0.08, P = 0.35, <em>r</em>espectively). The <em>r</em>elative abundances (mol%) of 14:0, 16:0, and 18:0 in <em>VLDL</em>-TG we<em>r</em>e weakly (<em>r</em> ≤ 0.35) associated with DNL, whe<em>r</em>eas the abundances of 16:1n-7, 18:1n-7, and 18:1n-9 we<em>r</em>e not associated. When the coho<em>r</em>t was split by median DNL, only the abundances of 14:0 and 18:0 in <em>VLDL</em>-TG could disc<em>r</em>iminate between subjects having high (11.5%) and low (3.8%) fasting hepatic DNL. Based on a subg<em>r</em>oup, FA ma<em>r</em>ke<em>r</em>s in total plasma TG, plasma choleste<em>r</em>yl este<em>r</em>s, plasma phospholipids, and <em>r</em>ed blood cell phospholipids we<em>r</em>e gene<em>r</em>ally not associated with DNL.</Abst<em>r</em>actText><Abst<em>r</em>actText>The usefulness of ci<em>r</em>culating FAs as ma<em>r</em>ke<em>r</em>s of hepatic DNL in healthy individuals consuming thei<em>r</em> habitual diet is limited due to thei<em>r</em> inability to disc<em>r</em>iminate clea<em>r</em>ly between individuals with low and high fasting hepatic DNL.</Abst<em>r</em>actText>

Cholesteryl esters (CE) exchange between lipoproteins through the action of cholesteryl ester transfer protein (CETP). Situations at high risk for atherosclerosis are often accompanied by an accelerated net mass CE transfer (CET) from high density lipoproteins (HDL) to very low (VLDL) and low density lipoproteins (LDL). However, the question as to whether the net mass CET is increased or decreased in non-insulin-dependent diabetes mellitus (NIDDM) has led to controversial data. To clarify this point, we have undertaken a detailed study of CET in 105 NIDDM patients by comparison with 17 control subjects. Net mass CET was approximately doubled in NIDDM. Plasma CETP activity and unidirectional CET from HDL to VLDL + LDL (CETHDL->>VLDL + LDL) or from VLDL + LDL to HDL (CETVLDL + LDL->>HDL) were measured under controlled lipoprotein concentrations using radioisotopic assays. No difference was observed in plasma CETP activity between NIDDM and controls. In NIDDM, CETHDL->>VLDL + LDL and CETVLDL + LDL->>HDL were decreased by 25% and 20%, respectively, as a consequence of alterations in lipoprotein compositions. Net mass CET was highly correlated with plasma triglyceride (TG) concentration (r = 0.66, P < 0.001) but not with that of LDL-cholesterol (r = 0.06, P>> 0.6). When TG levels were decreased following dietetic recommendations or insulinotherapy, the net mass CET was lowered accordingly. We conclude that net mass CET is accelerated in NIDDM in spite of a decreased unidirectional CETHDL->>VLDL + LDL. This results from a lowered CETVLDL + LDL->>HDL and from elevated TG concentration, and the latter probably reflects a concentration effect of VLDL.

OBJECTIVE

To observe the changes of C-reactive protein (CRP) level and its relationship with blood lipids, and the effects of fluvastatin on CRP and the lipids in patients with hyperlipidemia.

METHODS

Serum levels of cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C) and lipoprotein(a)[Lp(a)] were measured by enzyme assay, and plasma CRP level by immunonephelometry before and after fluvastatin treatment (20 mg/d for 4 weeks) in patients with hyperlipidemia.

RESULTS

CRP levels were above normal in 90.3% hyperlipidemia cases in spite of the various accompanying diseases. Fluvastatin treatment significantly reduced TC (-7.49%), TG (-14.32%), LDL (-13.88%), VLDL (-18.48%) and TC/HDL(-13.50%) levels (P<0.01), and also brought down Lp(a) concentration (-13.81%). CRP levels was very effectively reduced after the treatment (-15.92%, P<0.001). No association between basal CRP levels and basal lipids and Lp(a) concentrations was observed. Positive correlation of CRP, however, was observed after fluvastatin treatment with TC/HDL (r=0.62, P=0.041) and Lp(a) (r=0.320, P=0.011), while inverse relations were noted between CRP and HDL (r=-0.288, P=0.023).

CONCLUSIONS

CRP levels increases markedly in patients with hyperlipidemia, a fact that is independent of the accompanying diseases. In addition to modulating blood lipid levels, fluvastatin also reduces CRP level, the latter possibly serving as an independent predictive factor for atherosclerotic cardiovascular diseases and also as an indicator for estimating the effectiveness of the treatment.

We describe the characterization of a novel mutation in the low density lipoprotein receptor (LDL-R) gene in a patient with true homozygous familial hypercholesterolemia (FH). The combined use of denaturing gradient gel electrophoresis (DGGE) and sequencing of genomic DNA revealed a guanine to adenine base substitution at nucleotide position 1013 of the LDL-R cDNA. This point mutation results in a change from cysteine to tyrosine at amino acid residue 317 of repeat A of the epidermal growth factor (EGF) precursor homology domain. Binding, uptake and degradation of iodinated LDL in skin fibroblasts from the homozygous patient were less than 10% of normal. In contrast, binding, uptake and degradation of iodinated VLDL was reduced by only 60, 30, and 38%, respectively. Incubation of the patient's fibroblasts in the presence of cholesterol diminished the residual binding of VLDL by 50%, suggesting that the loss of the highly conserved cysteine at position 317 results in a LDL-R that fails to bind LDL, but retains some ability to bind VLDL by interacting with the apolipoprotein E. Both parents were heterozygous for the C317Y mutation. Interestingly, however, the father presented with markedly elevated levels of triglycerides and VLDL cholesterol, whereas his LDL cholesterol was unexpectedly low. The mother of the index patient had only slightly elevated LDL cholesterol. These observations testify to the biological complexity of genotype-environment interactions in individuals carrying mutations at the LDL-R locus and indicate that genetic analysis importantly complements the clinical and biochemical diagnosis of patients with hyperlipidemia.

UNASSIGNED

The objective of this study was to determine whether cardiovascular disease (CVD) risk factors and stress hormones are associated with cognitive performance in Mexican adolescents.

UNASSIGNED

This was a cross-sectional study including 139 Mexican adolescents 10-14 years old. Participants were divided into three categories: 0, 1-2, and ≥3 CVD risk factors. These factors included: high-density lipoprotein-cholesterol (HDL-C) <40 mg/dl; waist circumference (WC) ≥90th percentile for age and sex, systolic or diastolic blood pressure ≥90th percentile for age, sex, and height; and triacylglycerols (TGs) ≥110 mg/dl. Low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), total cholesterol, cortisol, and plasma catecholamines were measured as well. Furthermore, attention, memory, and executive functions were evaluated using a validated test for Spanish-speaking individuals (Neuropsi).

UNASSIGNED

Adolescents in the three risk categories did not show significant differences in Neuropsi test performance tasks; however, they presented different lipid and plasma norepinephrine concentrations. TG and VLDL-C were inversely associated with memory (r = -0.19, **p < .01). Multivariate regression analysis showed consistently that TG/HDL-C ratio was inversely related to attention-memory general score (standardized β = -0.99, t = -2.30, p = .023), memory (standardized β = -0.83, t = -2.08, p = .039), and attention-executive functions (standardized β = -1.02, t = -2.42, p = .017). Plasma epinephrine levels presented an inverse and weak relation to the attention-executive functions score (standardized β = -0.18, t = -2.19, p = .030).

UNASSIGNED

Cognitive performance is not completely dependent on the accumulation of risk factors, but instead on the combination of strong predictors of CVD like waist to height ratio, TG/HDL-C, and VLDL-C. Plasma norepinephrine and epinephrine have a stronger association with cognition and CVD risk than dopamine and cortisol.

We used discontinuous gradients of polyacrylamide gel to determine the high-density-lipoprotein (HDL) subfractions HDL2 and HDL3 of serum lipoproteins. Serum (40 microL) prestained with Sudan Black was electrophoresed in cylindrical tubes over successive layers of 3.5%, 6%, 13%, and 17.5% acrylamide gels in a Tris.glycine buffer (3-4 h, 300 V). Very-low- (VLDL) and low-density lipoprotein (LDL) were retained by the 3.5% and 6% gels. HDL2 was concentrated at the interface between the 13% and 17.5% gels, and HDL3 migrated into the 17.5% gel. The distribution between HDL2 and HDL3 was obtained by densitometric scanning. Application of the respective percentages to HDL cholesterol assayed after phosphotung-state-Mg2+ precipitation of VLDL and LDL gave calculated concentrations of HDL2 and HDL3 cholesterol. The calculated values for HDL2 cholesterol were in excellent agreement with those for HDL2 isolated by ultracentrifugation (r = 0.920 for n = 120 sera; differences nonsignificant by Student's paired t-test). Besides being highly discriminating, the method is rapid, easily performed, and economical.

Objective: To investigate the features of plaques of saphenous venous graft (SVG) with virtual histology intravascular ultrasound (VH-IVUS) in patients underwent coronary artery bypass graft surgery. Methods: From March 2016 to March 2018, a total of 45 patients ((64.4±7.9) years old, 88.9% male (40 cases)) with ischemic symptoms after coronary artery bypass graft surgery and with coronary artery angiography evidenced SVG stenosis greater than or equal to 50%, who received percutaneous coronary intervention in Tianjin chest hospital were continuously included in this study, and the clinical data were retrospectively analyzed. VH-IVUS was performed before PCI to analyze plaque composition. The patients were divided into no smoking group (21 cases) and smoking group (24 cases), no diabetes group (30 cases) and diabetes group (15 cases), normal very low density lipoprotein cholesterin (VLDL-C) group (24 cases) and elevated VLDL-C group (21 cases), stable angina pectoris group (5 cases) and acute coronary syndrome group (40 cases), plaque burden (PB) < 70% group (11 cases) and PB ≥ 70% group (34 cases), without thin-cap fibroatheroma group (35 cases) and thin-cap fibroatheroma group (10 cases), and plaque features were compared between different groups. Results: The graft age was (8.9±3.7) years.The stenosis degree of SVG lesions was 90 (90, 98) %. The minimum lumen diameter was 1.6 (1.5, 1.8) mm. The vessel cross-sectional area was (12.1±4.0) mm(2). The plaque area was 8.6 (5.7,12.0) mm(2). The minimum lumen area was 2.5 (2.1,3.3) mm(2). The plaque burden was (75.3±8.3)%. The fibrotic tissue (FI) ratio was (65.1±10.1)%, fibrofatty plaque (FF) ratio was 13.8 (5.4,25.3) %, necrotic core tissue (NC) ratio was 12.0 (5.4,24.0)%, and dense calcium tissue (DC) ratio was1.0 (0.2,3.8)% in SVG lesions. There were no significant differences in SVG plaque area, FI area,FF area,NC area,and DC area between no smoking group and smoking group, no diabetes group and diabetes group, and normal VLDL-C group and elevated VLDL-C group. SVG plaque volume was significantly higher in acute coronary syndrome group than in stable angina pectoris group (262.2 (148.5,401.2) mm(3) vs. 93.1 (50.6,155.9) mm(3),P=rea (10.1 (6.6,13.3) mm(2) vs. 5.0 (3.6,6.9) mm(2), P<rea(4.8 (3.2,6.8) mm(2) vs. 2.8 (1.9,3.0) mm(2), P<rea (1.15 (0.60, 2.07) mm(2) vs. 0.30 (0.10,0.90) mm(2), P=re significantly larger in PB ≥ 70% group than in PB < 70% group.The NC area (1.75(0.40,2.78) mm(2) vs. 0.60 (0.20,1.30) mm(2), P=rea (0.35 (0.10,0.50) mm(2) vs. 0.00 (0.00,0.10) mm(2), P=re significantly larger in thin-cap fibroatheroma group than that in without thin-cap fibroatheroma group. Spearman correlation analysis showed that the plaque area of SVG lesion was positively correlated with FF area (r=0.64, P<rea (r=0.43, P=rrelated with FF area (r=0.50, P<rea (r=0.33, P=0.028). Graft age was positively correlated with FF area (r=0.30, P=0.047). Conclusions: The main components of SVG plaque are fibrotic tissue, conversely, calcified tissue is rare in patients with SVG stenosis after coronary artery bypass graft surgery. Fibrofatty tissue is increased in the plaque in patients with PB ≥ 70%. The necrotic component is also increased in patients with thin-cap fibroatheroma. The fibrofatty component increases and the plaque tends to be unstable in proportion with increaing age of the graft in this patient cohort.

Normal human plasma HDL was applied to a column of heparin-Sepharose in the presence of MnCl(2) and three fractions were obtained by stepwise elution with increasing NaCl concentrations: a non-retained fraction (NR, 78% of protein) and two retained fractions (R(1) and R(2), 18 and 2.5% of protein, respectively). Both unesterified and esterified cholesterol increased from NR to R(1) to R(2) but the increment was more pronounced for unesterified cholesterol. ApoA-II to apoA-I ratio was-lower in R(1) compared to NR but R(1) contained more apoC than NR. ApoE increased from NR to R(1) to R(2) (0.07, 0.4, and 14% of protein in each fraction, respectively) while apoB was found only in R(2). Agarose gel electrophoresis and immunoadsorbers for apoB and apoE showed that R(2) consisted of two major lipoprotein populations, one containing apoB and some apoE and the other containing apoE and no apoB. Cholesteryl ester transfer between each HDL subfraction and VLDL in the presence of partially purified cholesterol ester transfer protein was studied. NR and R(1) gave the highest initial rates of transfer for labeled cholesteryl ester which were corroborated by significant mass transfer of cholesteryl esters. From these results, we concluded that there is no connection between cholesteryl ester transfer and apoE. On the other hand, transfer from R(2) to VLDL followed different kinetics with a high zero hour transfer but with subsequently lower rates when compared to NR and R(1). The cholesteryl ester transfer activity in R(2) was mainly due to the presence of apoE-containing lipoproteins whereas those containing apoB had minimal transfer activity. However, because this transfer of label was not translated into significant mass transfer of cholesteryl ester to VLDL, the apoE-containing lipoproteins appear involved mainly in the equilibration of cholesteryl esters.-Marcel, Y. L., C. Vézina, D. Emond, R. B. Verdery, and R. W. Milne. High density lipoprotein subfractions isolated by heparin-Sepharose affinity chromatography and their role in cholesteryl ester transfer to very low density lipoproteins.

We investigated whether freezing and storage of plasma altered alpha-tocopherol levels of whole plasma or the lipoprotein fractions derived from such plasma. Plasma from 24 men, at each of two collection periods, was frozen at -20 degrees C for six weeks, then high-density lipoproteins (HDL) were separated from low- plus very low-density lipoproteins (LDL-VLDL) by heparin affinity chromatography. Whole plasma and the lipoprotein fractions were analyzed for alpha-tocopherol content and compared to counterparts from fresh plasma. Freezing and storage did not reduce alpha-tocopherol levels of plasma or the lipoprotein fractions. alpha-Tocopherol values from fresh and frozen plasma were highly correlated for both plasma (period 1, r = 0.94; period 2, r = 0.93) and the LDL-VLDL fractions (periods 1 and 2, r = 0.97). Percent distribution of alpha-tocopherol between the two lipoprotein fractions was comparable for lipoproteins derived from fresh and frozen plasma. Under the storage conditions used in this study, plasma can be frozen for at least six weeks prior to lipoprotein fractionation with no detectable detrimental effects on alpha-tocopherol content of either plasma or lipoproteins.

The ligand-binding domain of the very low-density lipoprotein receptor (VLDL-R) contains eight cysteine-rich repeat sequences that have been postulated as ligand-binding sites. This is obviously different from that of low-density lipoprotein receptor (LDL-R) that includes seven similar repeats. To make clear the contribution of these repeats to ligand-binding and to explore the reason of both receptors' ligand-binding characteristic, the VLDL-R recombinants lacking different repeat(s) were constructed by oligonucleotide-directed mutagenesis and transfected into ldl-A7 cell. Ligand-binding results showed that repeat 1 and repeat 2 were the most important in binding with apoE-rich lipoprotein(VLDL and beta-VLDL). Repeat 3 and repeat 6 also important for binding VLDL. The results also showed that VLDL-R lacking LBRR ligand-binding properties. It suggests that LBRVLDL-R may responsible for both receptors' ligand-binding properties differences.

The mechanism leading to hyperlipidemia in the nephrotic syndrome is not fully understood but may be related in part to loss of high density lipoproteins in the urine of patients with nephrosis. To prove this hypothesis, we compared serum lipoprotein profiles with the excretion of high density lipoproteins in urine in 19 nephrotic patients. Serum cholesterol ranged from 19-152 (median value 45) mg/dl in very low density lipoproteins (VLDL), from 130-443 (median 186) mg/dl in low density lipoproteins (LDL) and from 19-64 (median 33) mg/dl in high density lipoproteins (HDL). Hyperlipoproteinemia was found in 17 patients, which was classified as phenotype IIa (Fredrickson) in 2, as phenotype IIb in 9 and as phenotype IV in 6 subjects. Two patients showed normal lipoprotein patterns. VLDL- and LDL-cholesterol were not found in detectable amounts in urine, whereas HDL-cholesterol was measured in low concentrations from 0.1-8.3 mg/24 h in all samples. There was no correlation between serum HDL-cholesterol and urinary HDL-cholesterol, but a positive correlation between serum LDL-cholesterol and urinary HDL-cholesterol (r = +0.54, p less than 0.05). However, the total amount of the daily urinary loss of HDL (less than 1% of total plasma HDL) seems not to be sufficient to explain hyperlipoproteinemia in the nephrotic syndrome.

Overproduction of VLDL (very-low-density lipoprotein) particles is an important cause of FCHL (familial combined hyperlipidaemia). It has been shown recently that VLDL production is driven by the amount of hepatic fat. The present study was conducted to determine the prevalence of fatty liver in relation to the different fat compartments and lipid parameters in FCHL. A total of 68 FCHL patients, 110 normolipidaemic relatives and 66 spouses underwent ultrasound of the abdominal region to estimate the amount of subcutaneous, visceral and hepatic fat. Skinfold callipers were used to measure subcutaneous fat of the biceps, triceps, subscapular and supra-iliacal regions. Fatty liver was observed in 18% of the spouses, 25% of the normolipidaemic relatives and 49% of the FCHL patients. After adjustment for age, gender and body mass index, the prevalence of fatty liver was significantly higher in FCHL patients compared with spouses [OR (odds ratio), 3.1; P=0.03], and also in the normolipidaemic relatives compared with spouses (OR, 4.0; P=0.02), whereas no differences were observed between FCHL patients and normolipidaemic relatives (OR, 0.8; P=0.58). In the normolipidaemic relatives and FCHL patients combined, both visceral fat mass and subcutaneous abdominal fat were independent predictors of fatty liver (P<0.001 for both fat compartments; FCHL status corrected). Of interest, fatty liver stages were correlated with both VLDL-apoB (apolipoprotein B) and VLDL-triacylglycerols (triglycerides) in a representative subset (n=69) of patients and relatives (r(2)=0.12, P=0.006; and r(2)=0.18, P=0.001 respectively). These results show that fatty liver is a central aspect of FCHL, i.e. patients and normolipidaemic relatives. Both visceral and subcutaneous adiposity contribute to its 3-4-fold higher risk in FCHL.

The metabolism of very low density lipoprotein (VLDL) from normolipemic (NTG) subjects, hypertriglyceridemic (HTG) subjects, and hypertriglyceridemic subjects treated with bezafibrate (BZ) was studied in cultured human skin fibroblasts. The binding, cell association, and proteolytic degradation of 125I-labeled lipoproteins and the capacity to regulate cellular sterol synthesis was determined with and without maximal stimulation of the lipoprotein by exogenous recombinant or plasmatic apolipoprotein (apo) E-3. The VLDL was separated into three density subfractions: I, II, and III. Multiple differences between HTG and NTG lipoproteins were found, which all reverted toward normal with therapy. Even in the presence of an optimal concentration of apo E-3, HTG-VLDL demonstrated 100% to 200% higher metabolic activities, indicating a better association or a better biological expression of apo E-3 at the surface of the lipoprotein. There was a strong and linear relationship between the cholesterol ester/protein ratios of the different VLDLs and their proteolytic degradations by the cells (r = 0.95). Thus, the composition/structure alterations of VLDL appear to determine their apo E-3-dependent cellular catabolism. In addition, HTG-VLDLs not enriched with apo E-3 exhibited a capacity to down-regulate cellular sterol synthesis independently of their uptake and degradation by the cells. This abnormality appeared to reflect the ability of the VLDL to donate cholesterol to the cells and was not observed in receptor-negative cells. Thus, HTG-VLDL is much more capable than NTG-VLDL of introducing cholesterol to cells by at least two mechanisms: 1) accelerated uptake and degradation and 2) direct transfer of cholesterol to the cells. Both processes are potentially atherogenic and are reversible when triglyceride-lowering therapy is instituted.