Biomedical subjects

S Lamon-Fava

Publications and source records attributed to S Lamon-Fava.

35 records · Page 2Linked to original sources

PubMed1994

Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid Research Clinics Coronary Primary Prevention Trial.

OBJECTIVE: To examine the relationship between elevated levels of lipoprotein(a) [Lp(a)] and coronary heart disease (CHD) risk in a prospective study. DESIGN: Nested case-control study. The cohort consisted of participants in the Lipid Research Clinics Coronary Primary Prevention Trial. SETTING: Lipid research clinics. PARTICIPANTS: The Lipid Research Clinics Coronary Primary Prevention Trial participants (n = 3806) were men, aged 35 to 59 years, with plasma cholesterol levels of 6.85 mmol/L (265 mg/dL) or greater, low-density lipoprotein cholesterol levels of 4.91 mmol/L (190 mg/dL) or greater, and triglyceride levels less than 3.39 mmol/L. Subjects were randomly assigned to either cholestyramine or placebo treatment. The Lp(a) levels were measured in plasma samples obtained prior to randomization in 233 cases (participants who developed CHD in the course of the study) and 390 matched CHD-free controls. A total of 96.95% of the subjects were white, 2.25% were black, and 0.80% were of other race. MAIN OUTCOME MEASURE: Coronary heart disease (either fatal or nonfatal) events during a follow-up of 7 to 10 years. RESULTS: The Lp(a) levels were significantly higher (21%) in cases than in controls (23.7 mg/dL [0.59 mmol/L] and 19.5 mg/dL [0.49 mmol/L], respectively; P < .02). This difference was still statistically significant (P < .01) after controlling for age, body mass index, cigarette smoking, blood pressure, low-density lipoprotein cholesterol level, and high-density lipoprotein cholesterol level. When subjects were divided by treatment, both cholestyramine-treated and placebo-treated CHD subjects had Lp(a) levels 20% to 22% greater than their matched controls. However, possibly because of smaller sample sizes, these differences were no longer statistically significant. CONCLUSIONS: Our data are consistent with the concept that an elevated Lp(a) level is an independent risk factor for CHD in hypercholesterolemic white men.

Adult↗

PubMed1994

Effects of dietary intakes on plasma lipids, lipoproteins, and apolipoproteins in free-living elderly men and women.

Plasma lipid and apolipoprotein (apo) A-I and B concentrations and habitual dietary intakes were determined in 306 free-living elderly individuals (119 men and 187 women, age range 60-100 y). Plasma lipid and apo A-I concentrations were significantly higher in women than in men. In older men, plasma triglyceride, total cholesterol, and apo B concentrations were significantly lower than in younger men, whereas a significant trend towards lower LDL-cholesterol concentrations was observed in older women. Energy intake and percent macronutrient intake were not influenced by age. Higher carbohydrate intake was associated with lower HDL cholesterol and apo A-I concentrations, whereas higher total fat intake was associated with higher apo A-I concentrations. Higher vitamin A intake was associated with higher plasma concentrations of HDL cholesterol and apo A-I. Our data indicate that both dietary and plasma concentrations of vitamin A, body mass index, age, and sex are important determinants of plasma lipid concentrations in the elderly.

Aged↗

PubMed1994

Effects of gender and menopausal status on the association of apolipoprotein E phenotype with plasma lipoprotein levels. Results from the Framingham Offspring Study.

Apolipoprotein (apo) E phenotype is an important genetic determinant of plasma low-density lipoprotein (LDL) cholesterol and apo B levels. We have determined apo E phenotype by isoelectric focusing and plasma lipid, lipoprotein cholesterol, apo A-I, apo B, and lipoprotein(a) levels, as well as LDL particle size, in 2258 men and women participating in the Framingham Offspring Study. Apo E phenotype (E2/2, E2/4, E3/2, E3/3, E3/4, and E4/4) was not associated with plasma lipoprotein(a) levels but was associated with plasma LDL cholesterol levels, apo B levels, and LDL size in men and with plasma total cholesterol, LDL cholesterol, and apo B levels in women. The average effect of the epsilon 2 allele was to lower plasma LDL cholesterol levels by 9.2 mg/dL in men and by 13.7 mg/dL in women, while the average effect of the epsilon 4 allele was to increase LDL cholesterol levels by 2.6 mg/dL in men and by 5.4 mg/dL in women. When men were divided into two groups according to their age (< 50 and > or = 50 years old), the average effect of the epsilon 2 allele was to lower plasma levels of LDL cholesterol by 10.2 mg/dL in younger men and by 7.5 mg/dL in older men. In premenopausal women, the average effect of the epsilon 2 allele was to lower LDL cholesterol by 8.2 mg/dL and, in postmenopausal women, by 20.4 mg/dL. An opposite effect of the epsilon 4 allele was observed: the epsilon 4 allele was associated with increases in plasma LDL cholesterol levels of 4.0 mg/dL in younger men and of 1.0 mg/dL in older men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study.

Plasma low density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B, the major protein constituent of LDL, were measured in 1,533 men (mean age 49 +/- 10 years) and 1,597 women (mean age 49 +/- 10 years) participating in the 3rd examination cycle of the Framingham Offspring Study. Mean plasma levels of LDL cholesterol and apoB were higher in men than in women (136 versus 132 mg/dl, P < 0.0001; and 109 versus 95 mg/dl, P < 0.0001, respectively). Increased age was associated with higher plasma LDL cholesterol and apoB levels, especially in women. After adjustment for age and body mass index, LDL cholesterol and apoB levels were still significantly higher in postmenopausal than in premenopausal women, indicating a hormonal effect on LDL metabolism. The associations between coronary heart disease (CHD) and LDL cholesterol, non-HDL cholesterol, apoB, and other plasma lipid and lipoprotein parameters were examined by dividing participants in four groups, based on approximate quartiles for these parameters. Elevated LDL cholesterol levels were not significantly associated with CHD in men, but were in women. This result, at variance with that of several longitudinal studies, is likely due to the cross-sectional design of our analysis. Elevated non-HDL cholesterol and apoB levels were significantly associated with the presence of CHD, in both males and females. A plasma apoB value > or = 125 mg/dl may be associated with an increased risk for CHD. Low plasma levels of HDL cholesterol were also significantly associated with CHD. Plasma triglyceride levels, age and body mass index were strong determinants of LDL cholesterol, non-HDL cholesterol, and apoB levels in men and women. In women, postmenopausal status and elevated blood pressure were also significantly associated with elevated levels of these parameters.

Adult↗

PubMed1994

Factors associated with low and elevated plasma high density lipoprotein cholesterol and apolipoprotein A-I levels in the Framingham Offspring Study.

A decreased high density lipoprotein (HDL) cholesterol level (< 35 mg/dl) has been shown to be a significant independent risk factor for coronary heart disease (CHD). Moreover, increased HDL cholesterol levels (> or = 60 mg/dl) are associated with a decreased CHD risk. Levels of HDL cholesterol and apoA-I, the major protein constituent of HDL, were measured in plasma from fasting participants in the Framingham Offspring Study (1,584 men and 1,639 women, mean age 49 +/- 10 years). In this population, an HDL cholesterol value < 35 mg/dl was observed in 18.2% of men and 3.8% of women, and these subjects had mean apoA-I levels of 104 and 106 mg/dl, respectively, and triglyceride levels of 234 and 261 mg/dl, respectively. CHD was observed in 14.2% of men and 14.5% of women in this category. An HDL cholesterol level > or = 60 mg/dl was observed in 11.7% of men and 39.3% of women, and these subjects had mean apoA-I levels of 182 and 185 mg/dl, respectively, and mean triglyceride levels of 81 and 75 mg/dl, respectively. CHD was noted in 2.7% of men and 1.9% of women in this category. HDL cholesterol levels were much more strongly related to triglycerides (r = -0.54 in men and -0.47 in women) than was apoA-I (r = -0.26 in men and -0.13 in women). The relationship between plasma HDL cholesterol and triglyceride levels was not linear. In both men and women, triglycerides, body mass index (BMI), and alcohol intake contributed significantly to HDL cholesterol and apoA-I variability.

Adult↗

PubMed1993

Physiologic benefits of a stress reduction program for healthy middle-aged Army officers.

Stress reduction programs (SRPs) can reduce morbidity and mortality in patients with coronary artery disease (CAD). This study evaluated the effect of an SRP on metabolic and hormonal risk factors for CAD. Twenty army officers participating in an SRP, Group I, and a comparison group of seventeen SRP nonparticipants, Group C, volunteered to undergo measurement of dehydroepiandrosterone-sulfate (DHEA-S), cortisol, DHEA-S/cortisol ratio, testosterone, apolipoprotein-A1, apolipoprotein-B, triglycerides, cholesterol, fibrinogen, and leukocyte count both before and after the SRP period. No differences in the changes in biochemical risk factors for CAD were found between participant and nonparticipant except for DHEA-S. While Group C had a marked reduction in DHEA-S levels, Group I had a small increase. Previous studies indicate DHEA-S is inversely associated with extent of CAD and age-adjusted DHEA-S levels below 3.78 mumol/l confer an increased risk for CAD mortality. SRP participation appears to effect DHEA-S levels, possibly partially accounting for the benefits observed in SRPs among CAD patients.

Adult↗

PubMed1993

Buspirone therapy for Type A behavior, hostility, and perceived stress in cardiac patients.

Hostility is considered to be a risk factor for coronary artery disease. Despite the findings of reduced serotonergic function and effectiveness of treatment with serotonergic agents in similar symptom complexes, there have been no attempts at using serotonergic psychopharmacologic agents to treat this population. We conducted an 8-week open trial of 10 type A, irritable men with coronary artery disease and no diagnosable psychiatric (axis I) condition to examine the effects of buspirone on these subjects. Buspirone appears to significantly reduce type A behavior, hostility, anxiety, impatience, and perceived stress.

Adult↗

PubMed1993

Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an atherogenic particle that structurally resembles a low density lipoprotein (LDL) particle but contains a molecule of apolipoprotein(a) attached to apolipoprotein B-100 by a disulfide bond. Because elevated plasma levels of Lp(a) have been shown to be an independent risk factor for coronary artery disease, it is important to define normal ranges for this lipoprotein. METHODS AND RESULTS: We have measured Lp(a) in 1,284 men (mean age, 48 +/- 10 years) and 1,394 women (mean age, 48 +/- 10 years) free of cardiovascular and cerebrovascular disease and not on medications known to affect lipids who were seen at the third examination cycle of the Framingham Offspring Study. Plasma Lp(a) levels were measured by an enzyme-linked immunosorbent assay, which uses a "capture" monoclonal anti-apo(a) antibody that does not cross-react with plasminogen, and a polyclonal anti-apo(a) antibody conjugated to horseradish peroxidase. The assay was calibrated to total Lp(a) mass. The Lp(a) frequency distribution was highly skewed to the right, with 56% of the values in the 0-10-mg/dL range. Mean plasma Lp(a) concentrations were 14 +/- 17 mg/dL in men and 15 +/- 17 mg/dL in women. Values of more than 38 mg/dL were above the 90th percentile and values of more than 22 mg/dL were above the 75th percentile in both men and women. CONCLUSIONS: We have determined mean Lp(a) levels for men and women participating in the Framingham Offspring Study. In this population, there was an inverse association between plasma levels of Lp(a) and triglycerides for both sexes (p < 0.006), but triglycerides accounted for only approximately 0.5% of the variation in Lp(a) levels. Associations of Lp(a) levels with total and LDL cholesterol levels were not significant after correction for the estimated contribution of Lp(a) cholesterol to total and LDL cholesterol. After controlling for age, Lp(a) values were 8% greater in postmenopausal women than in premenopausal women, but this difference was not statistically significant. Body mass index, alcohol consumption, cigarette smoking, use of beta-blockers or cholesterol-lowering medications, and use of drugs for the treatment of diabetes and hypertension were not correlated with Lp(a) levels.

Age Factors↗

PubMed1992

Psychological, behavioral and biochemical risk factors for coronary artery disease among American and Italian male corporate managers.

Differences in psychological, behavioral and biochemical risk factors for coronary artery disease (CAD) among male corporate managers of 2 countries (United States and Italy), with very different age-specific rates of mortality for CAD were evaluated. In all, 129 American (mean age 43 +/- 7 years) and 80 Italian (mean age 45 +/- 7 years) managers volunteered to participate in this study. Each subject was administered several questionnaires assessing various psychological and behavioral risk factors for CAD, and all 129 Americans and 55 of 80 Italians had their blood drawn between 8:00 and 9:30 AM after overnight fasting for the measurement of plasma levels of dehydroepiandrosterone-sulfate (DHEA-S), total cholesterol, triglycerides, and apolipoproteins A-I and B. Italian managers reported significantly more cynicism and hostility, and less enjoyment in leisure activities than did American ones. Furthermore, 40 Italian (51%) and only 18 American (14%) managers were smokers (this difference being statistically significant). Although no significant differences were found in factors positively related with CAD (cholesterol, triglycerides and apolipoprotein B), there were clear differences in parameters inversely correlated with the incidence of CAD. Italian managers had significantly lower levels of plasma DHEA-S and apolipoprotein A-I than did American ones. In conclusion, this study found that Italian managers had a significantly more unhealthy psychological and behavioral profile than did American ones, and had lower levels of those biochemical parameters (apolipoprotein A-I and DHEA-S) thought to have a protective role against development of CAD.

Administrative Personnel↗

PubMed1992

Induction of Calbindin-D28K by 1,25-dihydroxyvitamin D3 in cultured chicken intestinal cells.

Intestinal cells from chicken embryos were grown in chemically defined, serum-free medium. The majority of cultured cells exhibits an epithelial-like morphology. As demonstrated by indirect immunofluorescence, the epithelial cells, and not the contaminating fibroblasts, express Calbindin-D28K only after 1,25-dihydroxyvitamin D3, the hormonally active form of vitamin D, is added to the culture medium. The highly sensitive reverse transcriptase-polymerase chain reaction shows that both Calbindin-D28K mRNA and the corresponding primary unprocessed transcripts (pre-mRNA) are dramatically increased in cultured intestinal cells treated with 1,25-dihydroxyvitamin D3, thus indicating that Calbindin-D28K is induced by the increased rate of transcription of the corresponding gene.

Animals↗

PubMed1992

Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women.

The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, total cholesterol, very-low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-I and B levels and LDL particle size were assessed in 20 postmenopausal women with a previous hysterectomy and various forms of dyslipidemia (LDL cholesterol > or = 4.14 mmol/L [160 mg/dL] and/or HDL cholesterol < or = 1.03 mmol/L [40 mg/dL]). All subjects were studied while on a standard cholesterol-lowering diet, and were sampled in the fasting state before beginning estrogen therapy and after a mean of 13 weeks of estrogen therapy. Lipids were measured by standardized enzymatic techniques, apos were measured by enzyme-linked immunoassays, and LDL particle size was measured by gradient gel electrophoresis. Mean values for plasma lipid parameters (mmol/L) at baseline and during estrogen replacement were as follows: triglyceride, 2.11 and 2.75 (30% increase); total cholesterol, 7.45 and 6.52 (13% decrease); VLDL cholesterol, 1.09 and 1.22 (12% increase); LDL cholesterol, 5.09 and 3.70 (27% decrease); and HDL cholesterol, 1.27 and 1.58 (24% increase). Mean values for apo A-I were 163 and 254 mg/dL (56% increase), and for apo B they were 170 and 148 mg/dL (13% decrease). The LDL particle score was 4.09 and 4.52 (11% smaller). Changes in all parameters were statistically significant (P = .05) except for VLDL cholesterol. These data indicate that estrogen replacement is effective in decreasing LDL cholesterol and apo B concentrations and increasing HDL cholesterol and apo A-I concentrations in dyslipidemic postmenopausal women, but it should not be used in patients with baseline fasting triglyceride levels higher than 2.82 mmol/L (250 mg/dL) unless it is accompanied by a progestin. Our data indicate that this form of estrogen replacement could lower the risk of coronary artery disease (CAD) by more than 50% in these women, based on favorable alterations in plasma lipoproteins.

Aged↗

PubMed1992

Evolutionary distinct mechanisms regulate apolipoprotein A-I gene expression: differences between avian and mammalian apoA-I gene transcription control regions.

In mammals, the apolipoprotein (apo) A-I gene is expressed predominantly in liver and intestine, while in avian species it is expressed in all tissues. Although liver and intestine are the major sites of chicken apoA-I mRNA synthesis, there are appreciable amounts of apoA-I mRNA in kidney, ovary/testes, brain, lung, skeletal, and heart muscle. In this study, the nucleotide sequences of the chicken apoA-I gene and its 5' flanking region, as well as the sequences involved in the expression of this gene, have been determined. The gene spans 1.5 kilobases and contains 4 exons and 3 introns, closely resembling the mammalian apoA-I gene. To determine the sequences involved in the expression of the chicken apoA-I gene, plasmid constructs containing serial deletions of the 5' flanking region of the chicken apoA-I gene fused to the bacterial chloramphenicol acetyltransferase (CAT) gene were transfected in human hepatoma (HepG2), colon carcinoma (Caco2), epithelial (Hela), mouse embryonal fibroblast (NIH3T3) cells, and quail myoblasts (QMLA29). The shortest deletion construct, containing 60 bp of the 5' upstream region, was sufficient for maximal transcriptional activity in all cell lines tested. This region contains a short sequence (nucleotides -60 to -54) that is highly conserved in birds and mammals, and an Sp1 binding site. Although the sequence between nucleotides -232 and -101 of the 5' region of the chicken apoA-I gene is partially homologous to the hepatic cell-specific enhancer of the mammalian apoA-I gene (located between nucleotides -222 and -110 upstream of the human apoA-I gene transcription start site), this chicken sequence is transcriptionally inactive in HepG2 cells. These results suggest that differences in the cis-acting regulatory elements of the apoA-I gene play a fundamental role in determining the differences in the tissue-specific expression of this gene in avian and mammalian species.

Amino Acid Sequence↗

PubMed1991

The NHLBI Twin Study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a).

Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The intraclass correlation coefficient for apo A-I was significantly greater in MZ twins (0.56) than in DZ twins (0.37, P less than 0.05); however, apo A-I showed an unequal distribution in the two groups, with significantly greater total variance in DZ twins. Therefore the among-component estimate of genetic variance was applied, and the results indicated no significant heritability for apo A-I (P = 0.59). MZ and DZ twins had equal apo B variance. The intraclass correlation coefficient for apo B in MZ twins (0.71) was significantly higher than in DZ twins (0.25) (P less than 0.0001), indicating significant heritability for apo B. Plasma apo A-I levels were significantly correlated with alcohol intake (P less than 0.0001), body mass index (BMI, P less than 0.0001), and physical activity, while apo B levels were significantly correlated only with BMI (P less than 0.05). After plasma apo A-I and apo B concentrations were adjusted for all of these variables and for cigarette smoking, the analysis of variance and intraclass correlation coefficients remained virtually unchanged. The LDL type intraclass correlation coefficient was higher in MZ twins (0.58) than in DZ twins (0.32, P less than 0.005); however, greater total variance for this parameter in DZ twins was observed and after applying the among component estimate of genetic variance, no significant heritability of LDL type was observed. After adjustment for covariate effects the conclusions were not changed. Only 8.4% of MZ twin pairs, as compared with 26.7% of DZ twin pairs, were discordant for elevated lipoprotein(a) on gradient gels (P less than 0.0001). Our data indicate that there is a strong heritability for plasma apo B and lipoprotein(a), with only weak evidence for heritability of LDL type or plasma apo A-I levels within this population sample.

Aged↗

PubMed1989

Acute changes in lipid, lipoprotein, apolipoprotein, and low-density lipoprotein particle size after an endurance triathlon.

The effect of an endurance triathlon (2.4-mile swim, 112-mile bicycle ride, 26.2-mile run, in succession) on plasma total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I and B levels, and LDL particle size was determined in 34 male and six female participants 6 to 12 hours before and immediately after the completion of the triathlon. Plasma TG decreased significantly (70% decrease) in both men and women. In men the change in plasma TG was inversely associated with baseline TG values (P less than .0001). Plasma TC and LDL cholesterol did not change significantly in male athletes but decreased significantly in women. A significant increase in HDL cholesterol was observed in both men (18% increase, P less than .0001) and women (5% increase, P less than .01). In men the increase in HDL cholesterol was inversely correlated with the decrease in triglycerides (P less than .0002). Plasma apo A-I levels increased significantly only in the male group (P less than .005), whereas plasma apo B levels decreased significantly in both men and women (P less than .0005). LDL particle size increased in seven males, whereas in the remaining males and all females no change in LDL size was observed. The increase in LDL particle size in these seven subjects was associated with a greater decline in plasma TG compared with the remaining men (P less than .005) and women (P less than .03). These results indicate that prolonged strenuous physical exercise can induce acute modifications of plasma lipoproteins, which may in part be related to enhanced lipolysis.

Apolipoprotein A-I↗

PubMed1989

Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

Adult↗

PubMed1987

Secretion of apolipoprotein A-I in lipoprotein particles following transfection of the human apolipoprotein A-I gene into 3T3 cells.

Apolipoprotein A-I (apoA-I) is the major protein constituent of plasma high density lipoproteins (HDL). To examine apoA-I processing and secretion, the human apoA-I gene (2.2-kilobase PstI-PstI fragment) linked to the mouse metallothionein promoter was transfected by electroporation into NIH 3T3 fibroblasts along with the plasmid pSV2 neo, which confers neomycin resistance. Transfected cells were selected for neomycin resistance and screened for the ability to produce apoA-I by enzyme-linked immunosorbent assay. In the absence of lipids in the medium, selected 3T3 cells secreted apoA-I, mainly in the proprotein form, at density greater than 1.25 g/ml. Following incubation of cells with lipids, and subsequent washing with lipid-free medium, apoA-I was recovered in the HDL region (1.063-1.21 g/ml) as well as in the 1.21 g/ml infranatant. Examination of the HDL fraction by electron microscopy revealed round particles, 10-21 nm in diameter. These data indicate that human apoA-I secreted by transfected 3T3 fibroblasts can assemble into lipoprotein particles under the appropriate conditions.

Animals↗

PubMed1987

A novel cell line (Caco-2) for the study of intestinal lipoprotein synthesis.

Lipoprotein synthesis by the colonic adenocarcinoma cell line Caco-2 was investigated to assess the utility of this cell line as a model for the in vitro study of human intestinal lipid metabolism. Electron micrographic analysis of conditioned medium revealed that under basal conditions of culture post-confluent Caco-2 cells synthesize and secrete lipoprotein particles. Lipoproteins of density (d) less than 1.063 g/ml consist of a heterogeneous population of particles (diameter from 10 to 90 nm). This fraction consists of very low density lipoproteins (d less than 1.006 g/ml) and low density lipoproteins (d = 1.019-1.063 g/ml). Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S]methionine-labeled Caco-2 lipoproteins revealed that very low density lipoproteins contain apolipoprotein E (apoE) and C apolipoproteins, while low density lipoproteins contained apoB-100, apoE, apoA-I, and C apolipoproteins. The 1.063-1.21 g/ml density fraction contained two morphological entities, discoidal (diameter 15.6 +/- 3.9 nm) and round high density lipoprotein particles (diameter 10.2 +/- 2.3 nm). The high density lipoproteins contained apoA-I, apoB-100, apoB-48, apoE, and the C apolipoproteins. Using isoelectric focusing polyacrylamide gel electrophoresis newly secreted apoA-I was identified as pro-apoA-I. ApoE and apoC-III released by Caco-2 cells were highly sialylated. mRNA species for apoA-I, apoC-III, and apoE, but not apoA-IV were identified by Northern blot analysis. ApoA-I, apoB, and apoE were visualized in Caco-2 cells by immunolocalization analysis. This intestinal cell line may be useful for in vitro studies of nutritional and hormonal regulation of lipoprotein synthesis.

Adenocarcinoma↗