[Homocysteine and some lipid parameters in hypercholesterolemic children]

[Article in Polish]

Szymczak E, Chelchowska M, Radomyska B, Laskowska-Klita T.

Zaklad Biochemii i Diagnostyki Laboratoryjnej, Instytut Matki i Dziecka, Kasprzaka 17a, 01-211 Warszawa, Poland. medroz imid.med.pl

High serum homocysteine (tHcy) concentration is increasingly recognised as independent risk factor for atherosclerosis, early coronary heart disease (CHD) and other vascular diseases. It has been proved that adult cardiovascular disease begins in childhood. In the presented studies we determined concentrations of homocysteine, lipids and lipoproteins in plasma of hypercholesterolemic and normocholesterolemic children. In hypercholesterolemic children total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides were significantly higher, whereas HDL cholesterol and apolipoprotein A-I were lower in comparison to the control group. Total serum homocysteine in children with positive family history for cardiovascular disease CHD(+) was significantly higher than in the control groups, and in CHD(-) group. It was respectively 7.3 micromol/1 versus 5.45 micromol/l versus 5.21 micromol/l. The results obtained in our study indicate that in hypercholesterolemic children with positive family history for CHD, the concentration of tHcy can be considered as a separate predictive risk factor for premature cardiovascular disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11679680&dopt=Abstract cholesterol




Insulin injections enhance cholesterol gallstone incidence by changing the biliary cholesterol saturation index and apo A-I concentration in hamsters fed a lithogenic diet.

Dubrac S, Parquet M, Blouquit Y, Gripois D, Blouquit MF, Souidi M, Lutton C.

Laboratoire de Physiologie de la Nutrition, Batiment 447, Universite Paris-Sud, 91405 Orsay Cedex, France.

BACKGROUND/AIMS: A link between insulin and cholesterol gallstone disease has often been suspected but never demonstrated. The aim was to evaluate the direct implication of insulin in the gallbladder cholesterol gallstone formation process. METHODS: Hamsters fed with a soft-inducing lithogenic diet, enriched with sucrose, were injected daily, for 1 week, either with long-acting insulin or saline (controls). RESULTS: Insulin injections doubled the cholesterol gallstone incidence. The cholesterol saturation index (CSI) of bile significantly increased (+19%) and biliary apolipoprotein A-I (apo A-I) decreased, both in concentration (-71%) and the proportion relative to the total biliary proteins (-25%). No modifications in the biliary bile acid composition were noticed. Hepatic HMGCoA reductase activity was higher (+341%), CYP7A1 activity was lower (-52%), whereas CYP27A1 and CYP7B1 were not affected. The hepatic low-density liprotein (LDL)-receptor and SR-BI masses did not vary. The hepatic total cholesterol content increased (+42%). Fasting plasma phospholipid and triglyceride concentrations significantly decreased (-15 and -60%, respectively), but the cholesterol concentration remained constant. CONCLUSIONS: These results suggest that insulin injections enhance cholesterol gallstone incidence by increasing the CSI of bile and decreasing the concentration and proportion of a biliary anti-nucleating protein, apo A-I. Insulin modulates the major enzymes of cholesterol and bile acid metabolisms in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11690699&dopt=Abstract cholesterol




Endothelial nitric oxide synthase activity in aorta of normocholesterolemic rabbits: regional variation and the effect of estrogen.

Andersen MR, Stender S.

Department of Clinical Biochemistry, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900, Hellerup, Denmark. maand gentoftehosp.kbhamt.dk

OBJECTIVE: Several animal studies suggest that nitric oxide (NO) produced by the endothelium attenuates arterial cholesterol accumulation. In the present study we have asked the following questions: (1) is the regional variation in aortic cholesterol accumulation in hypercholesterolemic rabbits preceded by a regional variation in endothelial NO synthase (eNOS) activity in normocholesterolemic rabbits, and (2) is the antiatherogenic effect of estrogen in hypercholesterolemic rabbits preceded by a higher eNOS activity in normocholesterolemic rabbits. METHODS: The eNOS activity was determined by conversion of 14C-L-arginine to 14C-L-citrulline in freshly isolated endothelial cells of aorta in normocholesterolemic rabbits. In the regional variation study, 16 male and eight female rabbits were used. In the estrogen study, ovariectomized female rabbits were subcutaneously injected three times weekly with either 17beta-estradiol (n=7) or vehicle (n=7) for 18 weeks. RESULTS: In the regional variation study, the atherosclerosis prone aortic arch showed a significant lower eNOS activity than the more resistant abdominal aorta in both male (P<0.0001) and female (P<0.05) rabbits. In the estrogen study, the eNOS activity in the aortic arch and upper thoracic aorta was significantly higher in the estrogen than in the vehicle rabbits (P<0.05). In the lower thoracic aorta, however, the eNOS activity was the same. CONCLUSION: The findings suggest that a high NO production in the luminal endothelium of the arterial wall precedes a low cholesterol accumulation during a subsequent period of hypercholesterolemia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10869546&dopt=Abstract cholesterol




Serum leptin levels in patients with hyperlipidemias.

Haluzik M, Fiedler J, Nedvidkova J, Ceska R.

3rd Medical Department, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. mhalu lf1.cuni.cz

Leptin is a protein hormone produced by adipocytes that reflects the body fat content. The aim of our study was to compare serum leptin levels in randomly selected untreated males and females with hypercholesterolemia and combined hyperlipidemia and in healthy control subjects matched for age and body mass index and to study the relations between leptin and serum lipids and lipoproteins. No statistically significant differences in serum leptin levels were found between the male control group (5.26 +/- 2.81 ng/mL(-1)) and the male group with hypercholesterolemia (8.16 +/- 3.85 ng/mL(-1)) or combined hyperlipidemia (7.51 +/- 4.83 ng/mL(-1)) and between the female control group (13.0 +/- 8.12 ng/mL(-1)) and the female group with hypercholesterolemia (15.36 +/- 8.89 ng/mL(-1)) or combined hyperlipidemia (18.63 +/- 10.15 ng/mL(-1)). Leptin concentration in male group with hypercholesterolemia did not differ significantly from the female control group; in the other male groups, leptin levels were significantly lower than those of the other female groups. Serum leptin levels in all studied groups except for the male group with hypercholesterolemia positively correlated with body mass index. Serum leptin levels correlated negatively with high-density lipoprotein cholesterol in the female group with hypercholesterolemia (r = -0.67, P < 0.01) and the male group with combined hyperlipidemia (r = -0.56, P < 0.01). A positive correlation between serum leptin and high-density lipoprotein cholesterol (r = 0.67, P < 0.01) and between leptin and lipoprotein (a) (r = 0.71, P < 005) was found in female group with combined hyperlipidemia. No other significant relationships between leptin and serum lipids or lipoproteins were found. We conclude that serum leptin levels in patients with hyperlipidemias do not significantly differ from those healthy control subjects matched by age and body mass index.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10869898&dopt=Abstract cholesterol




Comparison of fasting and postprandial plasma lipoproteins in subjects with and without coronary heart disease.

Schaefer EJ, Audelin MC, McNamara JR, Shah PK, Tayler T, Daly JA, Augustin JL, Seman LJ, Rubenstein JJ.

Lipid and Heart Disease Prevention Program, New England Medical Center, Boston, Massachusetts, USA. eschaefer hnrc.tufts.edu

Plasma lipoprotein levels, including remnant-like particle (RLP) cholesterol and RLP triglycerides, were assessed in fasting (12 hours) and postprandial (PP) (4 hours after a fat-rich meal) states in 88 patients with coronary heart disease (CHD) and 88 controls. All lipoproteins were assessed by direct methods. We hypothesized that patients with CHD would have greater percent increases in their triglyceride levels, RLP cholesterol, and RLP triglycerides, in response to a fat-rich meal. In the fasting state, triglycerides, RLP cholesterol, RLP triglycerides, and low-density lipoprotein (LDL) cholesterol levels were all significantly higher in cases versus controls by 51%, 35%, 39%, and 40%, respectively. These levels were 57%, 37%, 64%, and 37% higher in the PP state, respectively. Mean high-density lipoprotein (HDL) cholesterol values were 27% lower in cases in both the fasting and PP states. After eating, triglycerides, RLP cholesterol, and RLP triglycerides increased 64%, 71%, and 290% in controls, respectively, whereas in cases these levels increased by 71%, 94%, and 340%, respectively (all p <0.0001). Percent increases in the PP state were not significantly different in cases versus controls. Following the fat-rich meal, LDL and HDL cholesterol decreased by 5% and 4% in controls, and by 7% and 6% in patients, with no significant difference in percent changes between groups. Fasting values correlated very highly with PP values for all parameters (all p <0.0001). Our data indicate that although patients with CHD have higher fasting and PP levels of triglycerides, RLP cholesterol, and RLP triglycerides than controls, the response (percent increase) to a fat-rich meal is comparable in both groups. Thus, a feeding challenge is not essential for assessment of these lipoproteins. Moreover, it is not necessary to obtain a fasting sample to assess direct LDL and HDL cholesterol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11703957&dopt=Abstract cholesterol




Estradiol esterification in the human preovulatory follicle.

Cigliano L, Spagnuolo MS, Dale B, Balestrieri M, Abrescia P.

Dipartimento di Fisiologia Generale ed Ambientale, Universita di Napoli Federico II, Via Mezzocannone 8-80134 Napoli, Italy.

In the preovulatory follicle, the LH surge stimulates progesterone production, reduces estradiol synthesis, and scales up the permeability of the blood-follicle barrier. The purpose of this study was to investigate whether the extent of these changes is correlated with the levels of estradiol, estradiol esters, and cholesteryl esters in the follicular fluid. The follicular levels of progesterone, estradiol, estradiol linoleate, cholesterol, and cholesteryl linoleate were measured by HPLC. The estradiol linoleate/estradiol ratio, which reflects the efficiency of in vivo estradiol esterification, and the cholesteryl linoleate/cholesterol ratio were calculated and found negatively correlated. The estradiol level was positively correlated with the cholesteryl linoleate/cholesterol ratio while negatively correlated with the estradiol linoleate/estradiol ratio. The in vitro activity of lecithin-cholesterol acyltransferase, the enzyme esterifying both cholesterol and estradiol, was assayed by incubating the fluid with labeled substrates. This activity was not correlated with either the estradiol linoleate/estradiol or the cholesteryl linoleate/cholesterol ratio. The enzyme K(m) and V(max) values were lower with estradiol than with cholesterol. Higher estradiol linoleate/estradiol ratios and lower cholesteryl linoleate/cholesterol ratios were associated with higher level of Haptoglobin penetration into the follicle. This level, which was determined by ELISA, was found increased with increased progesterone concentration and, therefore, used as a marker of the LH-stimulated permeability of the blood-follicle barrier. Our data suggest that early preovulatory follicles contain more cholesteryl esters and less estradiol esters than follicles closer to ovulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11711117&dopt=Abstract cholesterol




Apo(B)-dependent dyslipidemic phenotypes in type 1 diabetic patients.

Wagner AM, Ordonez-Llanos J, Hernandez M, Luis Sanchez-Quesada J, Blanco-Vaca F, Rigla M, de Leiva A, Perez A.

Department of Endocrinology and Nutrition, Hospital Sant Pau, Autonomous University of Barcelona, 08025, Barcelona, Spain

Background: The prevalence of apo(B)-dependent dyslipidemic phenotypes, which are associated with cardiovascular disease, is increased in normocholesterolemic type 2 diabetic patients. Our aim was to determine the impact of including apo(B) in the evaluation of normocholesterolemic type 1 diabetic patients. Methods: A total of 123 type 1 diabetic patients (47% male, age 36.6+/-12.5 years) were included. The apo(B) cut-off point (1.14 g/l) was obtained from a group of 53 normolipidemic control subjects of similar age and gender distribution; for low density lipoprotein cholesterol (LDLc), triglycerides, and high density lipoprotein cholesterol (HDLc), we used the cut-off points recommended by the National Cholesterol Education Program. LDLc was determined by ultracentrifugation or Friedewald's equation, depending on triglyceride concentrations, and apo(B) by immunoturbidimetry. Results: A total of 113 (92%) type 1 diabetic patients were normocholesterolemic, and 13% of these were dyslipidemic. The frequency of hyperapo(B) was similar in normocholesterolemic patients and controls (6.2 vs. 9.4%, respectively). Diabetic patients with hyperapo(B) had poorer glycemic control, higher total cholesterol, triglycerides, and LDLc, and a lower HDLc and LDLc/apo(B) ratio. Conclusions: Unlike type 2 diabetes, type 1 diabetes is not associated with an increased prevalence of hyperapo(B)-dependent dyslipidemic phenotypes. Thus, only in patients with poor glycemic control who display other components of diabetic dyslipidemia, typical for type 2 diabetes, does determining apo(B) concentrations provide additional information in type 1 diabetes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11711272&dopt=Abstract cholesterol




Lipoprotein (a), cholesterol and triglycerides in women with venous thromboembolism.

McColl MD, Sattar N, Ellison J, Tait RC, Walker ID, Packard CJ, Greer IA.

Department of Haematology, Royal Infirmary, Glasgow, UK. mmccoll1 aol.com

Plasma concentrations of lipoprotein (a), total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglyceride were measured in 62 women who had suffered an episode of objectively confirmed venous thromboembolism (VTE) at < or = 50 years of age, and in 98 age-matched female controls. The mean body mass index (BMI) of cases was significantly (P < 0.001) higher than that of controls. Plasma triglyceride was significantly higher, and total cholesterol/LDL- and HDL-cholesterol significantly lower, in cases compared with controls. After adjustment for BMI, the plasma total cholesterol and LDL-cholesterol remained significantly lower in cases. No significant differences in mean plasma lipoprotein (a) levels were identified between cases and controls. Lipoprotein (a) does not appear to be significantly associated with the development of VTE in young women. The increased risk of VTE in obese subjects may be mediated, at least in part, via hypertriglyceridaemia, which has previously been demonstrated to have effects on levels of coagulation factors, natural anticoagulants, and plasminogen activator inhibitor type 1.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10870800&dopt=Abstract cholesterol




Lipid and acute-phase protein alterations in HIV-1 infected patients in the early stages of infection: correlation with CD4+ lymphocytes.

Treitinger A, Spada C, da Silva LM, Hermes EM, Amaral JA, Abdalla DS.

Clinical Analysis Department, Health Sciences Center, Santa Catarina Federal University, Florianopolis, SC, Brazil. aricio ufsc.br

Lipid and acute-phase protein alterations have been described in various infection diseases, and they have been recorded during the early stages of HIV infection. Lipid and acute-phase protein profiles also have been correlated with cellular immunological abnormalities. To document these correlations during HIV infection, we studied 75 HIV-infected patients and 26 HIV-negative controls. Patients were classified according to the criteria proposed by the Walter Reed Army Institute: as WR-1 (CD4 lymphocytes, 1154 +/- 268/mm3), WR-2 (CD4, 793 +/- 348/mm3) and WR3/4 (CD4, 287+/-75 mm3). Triglycerides, total cholesterol and HDL-cholesterol concentrations were measured by enzymatic methods. Immunoglobulins (IgA and IgG) and acute-phase proteins (haptoglobin, alpha1-acid glycoprotein, C-reactive protein and transferrin) were determined by immunonephelometry. Haptoglobin levels were significantly increased in HIV-positive patients and correlated with the progression of HIV-infection (control<WR1<WR2<WR3/4). WR-2 and WR-3/4 patients had lower total cholesterol, HDL-cholesterol, and albumin concentrations, however, alpha1-acid glycoprotein and IgA levels were higher, when compared to HIV-negative controls. Elevated triglyceride levels (1.51+/-0.75 mmol/L) were found only in WR3/4 patients, when compared to the control individuals (1.05+/-0.04 mmol/L). No differences were found in transferrin and C-reactive protein concentrations among the studied groups. CD4+ lymphocyte counts were inversely correlated with triglycerides, IgA, alpha1-acid glycoprotein and haptoglobin, and they were positively correlated with albumin, total cholesterol and HDL-cholesterol. Multiple linear regression analysis showed that increased haptoglobin and IgA levels were the best predictive variables of a decreasing CD4+ lymphocyte count. In conclusion, our data showed that: 1) a decrease in total cholesterol, HDL-cholesterol and albumin levels occurred earlier than hypertriglyceridemia in the course of HIV infection; 2) increased levels of haptoglobin occurred earlier than that of alpha1-acid glycoprotein and IgA; 3) haptoglobin and IgA were the best predictive variables of a decreasing CD4+ lymphocyte count. Decreases in HDL-cholesterol and albumin levels with increases in haptoglobin, alpha1-acid glycoprotein, IgA, and triglycerides levels are indications of disease progression in HIV-infected patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11712964&dopt=Abstract cholesterol