retinol-palmitate and Arteriosclerosis

Topics: Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Arteriosclerosis; Biomarkers; Blood Chemical Analysis; Breath Tests; Cholesterol; Coronary Disease; Diterpenes; Electrophoresis, Polyacrylamide Gel; Humans; Hyperlipidemias; Lipoproteins; Receptors, LDL; Retinyl Esters; Triglycerides; Vitamin A

The effect of gemfibrozil on postprandial lipoprotein metabolism was investigated in a 12-week, randomized, double-blind, placebo-controlled trial in 20 non-insulin-dependent diabetic patients with moderate hypertriglyceridemia. The patients were given a meal containing 78 g of fat and 345,000 units of vitamin A to label chylomicrons and their remnants. Plasma obtained at various times during the fat-load test was separated into six fractions by gradient-density ultracentrifugation. Gemfibrozil reduced the postprandial triglyceride response, measured as the area under the time-dependent concentration curve, on average by 32% in whole plasma, by 38% in the Svedberg flotation unit (Sf) 1,100-3,200 chylomicron fraction, by 36% in Sf 400-1,100 chylomicrons, and by 38% in the Sf 60-400 lipoproteins. Retinyl palmitate, a measure of intestinally derived particles, was reduced in plasma by 34%, in Sf 1,100-3,200 by 46%, in Sf 400-1,100 by 44%, and in Sf 60-400 by 37%. All these reductions were significant in comparison with the placebo group. Particles with Sf < 60 were not significantly affected. In contrast to earlier observations in healthy subjects, no significant negative correlations existed between postprandial lipemia and high density lipoprotein cholesterol or the postheparin lipoprotein lipase activity. The reduction of the potentially atherogenic chylomicron remnants may decrease the risk of atherosclerosis in non-insulin-dependent diabetes mellitus, a hypothesis that awaits testing in prospective studies.

Topics: Arteriosclerosis; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diterpenes; Female; Food; Gemfibrozil; Humans; Lipids; Lipoproteins; Male; Middle Aged; Retinyl Esters; Triglycerides; Vitamin A

Postprandial lipemia after an oral fat challenge was studied in middle-aged men with visceral obesity. The two groups had similar plasma cholesterol levels, but obese subjects had higher levels of plasma triglyceride and reduced amounts of high-density cholesterol. Fasting plasma insulin was fourfold greater in obese subjects because of concomitant insulin resistance, with a calculated HOMA score of 3.1 +/- 0.6 vs. 0.8 +/- 0.2, respectively. Plasma apolipoprotein B(48) (apoB(48)) and retinyl palmitate (RP) after an oral fat challenge were used to monitor chylomicron metabolism. Compared with lean subjects, the fasting concentration of apoB(48) was more than twofold greater in obese individuals, suggestive of an accumulation of posthydrolyzed particles. After the oral lipid load, the incremental areas under the apoB(48) and RP curves (IAUC) were both significantly greater in obese subjects (apoB(48): 97 +/- 17 vs. 44 +/- 12 microg.ml(-1). h; RP: 3,120 +/- 511 vs. 1,308 +/- 177 U. ml(-1). h, respectively). A delay in the conversion of chylomicrons to remnants probably contributed to postprandial dyslipidemia in viscerally obese subjects. The triglyceride IAUC was 68% greater in obese subjects (4.7 +/- 0.6 vs. 2.8 +/- 0.8 mM. h, P < 0.06). Moreover, peak postprandial triglyceride was delayed by approximately 2 h in obese subjects. The reduction in triglyceride lipolysis in vivo did not appear to reflect changes in hydrolytic enzyme activities. Postheparin plasma lipase rates were found to be similar for lean and obese subjects. In this study, low-density lipoprotein (LDL) receptor expression on monunuclear cells was used as a surrogate marker of hepatic activity. We found that, in obese subjects, the binding of LDL was reduced by one-half compared with lean controls (70.9 +/- 15.07 vs. 38.9 +/- 4.6 ng LDL bound/microg cell protein, P = 0.02). Because the LDL receptor is involved in the removal of proatherogenic chylomicron remnants, we suggest that the hepatic clearance of these particles might be compromised in insulin-resistant obese subjects. Premature and accelerated atherogenesis in viscerally obese, insulin-resistant subjects may in part reflect delayed clearance of postprandial lipoprotein remnants.

Topics: Apolipoprotein B-48; Apolipoproteins B; Arteriosclerosis; Body Constitution; Body Mass Index; Cholesterol; Cholesterol, HDL; Chylomicrons; Dietary Fats; Diterpenes; Food; Humans; Hyperlipidemias; Insulin; Insulin Resistance; Kinetics; Lipase; Lipoproteins, LDL; Male; Middle Aged; Obesity; Receptors, LDL; Retinyl Esters; Triglycerides; Viscera; Vitamin A

Magnesium (Mg) fortification of drinking water succeeded in inhibition of atherogenesis development in a transgenic model of atherosclerosis-prone mice fed a high-cholesterol content diet. In order to delineate possible mechanisms of action of the anti-atherogenic effect of Mg, the involvement of LDL oxidation was studied. We determined the susceptibility of LDL to Cu+2 oxidation, anti-oxidized LDL antibody levels, and liver content of retinol and retinyl-palmitate. In order to study another possible mechanism we tested platelets interaction with extracellular matrix in both male and female mice with or without Mg fortification of drinking water. No difference was found in susceptibility of LDL to undergo oxidation. Female mice that received Mg had decreased anti-oxidized LDL antibody levels compared with control female mice, while there was no significant difference among male groups. On the other hand, only in the male group with Mg was a higher content of retinol and retinyl-palmitate found in the livers. Platelets coverage area on extracellular matrix was similar between groups. These results suggest that Mg might affect LDL oxidation, and thus atherogenesis.

Topics: Animals; Antibodies; Antioxidants; Arteriosclerosis; Cholesterol, LDL; Copper; Diet, Atherogenic; Disease Models, Animal; Diterpenes; Female; Humans; Lipoproteins, LDL; Liver; Magnesium; Male; Mice; Mice, Transgenic; Receptors, LDL; Retinyl Esters; Vitamin A

Blood lipid alterations after a fatty meal may be atherogenic, but there is little information regarding their associations with disease independent of fasting lipids. Asymptomatic atherosclerosis cases (n = 229) and 373 control subjects free of atherosclerosis, as defined by carotid intima-media thickness on ultrasound images, were given a fatty meal with vitamin A, followed by 3.5- and 8-hour measurements of triglycerides (TGs), TG-rich lipoprotein TGs, apoproteinB48, and retinyl palmitate. Among white men and women but not among blacks, case status was associated with greater postprandial responses of TGs and TG-rich lipoprotein TGs, but only in nonobese persons (body mass index < 30 kg/m2). The associations were strong and significant after controlling for coronary risk factors (odds ratio, approximately 2.0) and fasting TGs (odds ratio, 1.5). Associations with other postprandial lipid measurements did not persist after controlling for fasting lipids. Elevated postprandial TGs appear to be an independent risk factor for carotid intimal thickening in nonobese whites. The lack of such a relation in obese subjects and the lipid profile they manifest suggest that postprandial TGs must be accompanied by accumulation of TG-rich lipoprotein remnants to be atherogenic.

Topics: Apolipoprotein B-48; Apolipoproteins B; Arteriosclerosis; Black People; Carotid Artery Diseases; Carotid Stenosis; Coronary Disease; Dietary Fats; Diterpenes; Female; Humans; Male; Middle Aged; Obesity; Retinyl Esters; Triglycerides; Vitamin A; White People

From the cohort taking part in the Atherosclerosis Risk in Communities (ARIC) study, a multicenter investigation of atherosclerosis and its sequelae in women and men ages 45-64 years, a sample of 145 subjects with significant carotid artery atherosclerosis but without clinically recognized coronary heart disease was identified along with 224 group-matched control subjects. The aim of this paper is to measure the association of the apolipoprotein (apo) E polymorphism with the prevalence of significant carotid artery atherosclerotic disease (CAAD) after considering the contribution of established risk factor variables. The first model used a stepwise selection procedure to define a group of significant physical and lifestyle characteristics and a group of significant plasma lipid, lipoprotein, and apolipoprotein variables that were predictive of CAAD status in this sample. Those variables selected included age (years), body mass index (BMI; kg/m2), consumption of cigarettes (CigYears; number of cigarettes/d x the number of smoking years), hypertension status, high-density lipoprotein (HDL)-cholesterol (mg/dl), total cholesterol (mg/dl), and Lp[a] (micrograms/ml). The second model was built by forcing into the equation an a priori set of demographic, anthropometric, and lipoprotein variables, which were age, BMI, CigYears, hypertensive status, LDL-cholesterol, and HDL-cholesterol. In both models, the apo E genotype epsilon 2/3 was related to CAAD status. For both models, the estimated odds ratio of being a CAAD case associated with the apo E genotype epsilon 2/3 was > 2:1. The mechanism of the observed association between the epsilon 2/3 genotype and carotid atherosclerosis is unknown, but it is likely due to the known effects of the E2 isoform in causing delayed clearance of triglyceride-rich lipoproteins.

Topics: Adult; Apolipoproteins E; Arteriosclerosis; Carotid Arteries; Case-Control Studies; Cohort Studies; Diterpenes; Fasting; Female; Humans; Life Style; Lipids; Lipoproteins; Male; Models, Biological; Multicenter Studies as Topic; Polymorphism, Genetic; Prevalence; Regression Analysis; Retinyl Esters; Vitamin A

This study investigated the antioxidant contribution of vitamin A in protecting human low density lipoprotein (LDL) against copper-stimulated oxidation. The presence of small amounts of retinol (0.033 +/- 0.012 nmol/mol LDL) and retinyl palmitate (0.036 +/- 0.021 nmol/mol LDL) was routinely ascertained in the LDL. A single oral supplementation with 20,000 IU vitamin A caused a two- to three-fold increase of retinol and retinyl palmitate in the LDL isolated 8 h after the supplementation. In comparison to autologous-control LDL, vitamin A-enriched LDL were more resistant to oxidation, as expressed both by a clear delay in the onset of lipid peroxidation and by a reduction of the rate of conjugated diene hydroperoxide production during the propagation phase. The calculated incremental increase in the lag phase produced by 1 mol retinol per mol LDL is about 1000 min, suggesting that retinol is more potent than alpha-tocopherol in LDL. Oxidation experiments carried out with LDL isolated from plasma incubated in vitro with either retinol or retinyl palmitate indicated that retinol does lengthen the lag phase, whereas retinyl palmitate can slow the rate of peroxyl chain propagation, without affecting the duration of the lag phase. Temporal disappearance of retinol and retinyl palmitate, followed in comparison with that of alpha-tocopherol and beta-carotene, indicated that the reactivity of the antioxidants with lipoperoxyl radicals was in the sequence alpha-tocopherol, retinol, beta-carotene, and retinyl esters. Although the detailed antioxidant mechanism remains to be elucidated, these results suggest that LDL-associated vitamin A can play a role in maintaining the antioxidant status of LDL during oxidative stress in vivo.

Topics: Adult; Antioxidants; Arteriosclerosis; Copper; Diterpenes; Female; Free Radicals; Humans; In Vitro Techniques; Kinetics; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Retinyl Esters; Vitamin A

Postprandial lipoprotein metabolism may play an important role in the development of atherosclerosis. It is widely believed that in healthy octogenarians, the atherogenic process occurs very slowly. In the present study, postprandial lipoprotein metabolism was examined in 14 octogenarian subjects (mean age, 84 +/- 4.2 years) and 19 younger controls (mean age, 50 +/- 4.8 years) using the vitamin A-fat loading test, in which intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Results indicated that mean peak chylomicron remnant RP levels and the areas below the chylomicron remnant RP curve were significantly lower in the octogenarian group than in the controls (625 +/- 329 vs 1321 +/- 688 micrograms/L and 3740 +/- 1078 vs 6162 +/- 1063 micrograms/L.h, respectively; p < .0001). No differences were found between the two groups in chylomicron RP levels or in lipolytic activity. The study suggests that octogenarians do not exhibit the decrease in chylomicron lipolysis that usually accompanies aging. In addition, these subjects have significantly lower levels of chylomicron remnants in the circulation. Since accumulation of these particles has been implicated in the development of atherogenesis, our findings may indicate a major mechanism of atherosclerosis prevention in healthy octogenarians.

Topics: Aged; Aged, 80 and over; Apolipoproteins E; Arteriosclerosis; Chylomicrons; Diterpenes; Eating; Humans; Lipids; Lipolysis; Lipoproteins; Retinyl Esters; Triglycerides; Vitamin A

Ten subjects from the Forsyth County, North Carolina, and Washington County, Maryland, field centers in the Atherosclerosis Risk in Communities Study had two fat tolerance tests within a 10-day period from September 1988 to February 1989 to determine the reproducibility of markers for postprandial lipemia. No significant differences between visits were found in fasting mean plasma lipids, lipoproteins, and apolipoproteins. Postprandial triglycerides and retinyl palmitate were measured at 3.5 and 9.0 hours after the test meal in whole plasma. There were no significant differences in the mean levels of these analytes between visits. The correlation of triglycerides between repeat visits at 9.0 hours (r = 0.87) was stronger than in fasting samples (r = 0.67) or at 3.5 hours (r = 0.69). The mean plasma retinyl palmitate level at 3.5 hours was 15% higher than at the 9.0-hour level. The correlation of repeat measures of retinyl palmitate at 9.0 hours (r = 0.94) was much stronger than at 3.5 hours (r = 0.79). In conclusion, estimates of reliability in postprandial measurements of 9.0-hour triglycerides and retinyl palmitate levels were as strong as fasting lipid measurements of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol, and both postprandial triglyceride measurements exceeded that of fasting triglyceride (r = 0.67).

Topics: Apolipoproteins; Arteriosclerosis; Cholesterol; Dietary Fats; Diterpenes; Fasting; Female; Humans; Male; Maryland; Middle Aged; North Carolina; Pilot Projects; Reproducibility of Results; Retinyl Esters; Triglycerides; Vitamin A

Topics: Arteriosclerosis; Chromatography, Gel; Chylomicrons; Dietary Fats; Diterpenes; Humans; Lipoproteins; Lipoproteins, LDL; Reference Values; Retinyl Esters; Triglycerides; Vitamin A