Interrelationships between the concentration and size of the largest high-density lipoprotein subfraction and apolipoprotein C-I in infants at birth and follow-up at 2-3 months of age and their parents.

BACKGROUND: Lipoprotein subfractions in infants may predict the risk of cardiovascular disease factors in children. OBJECTIVE: To examine the relationships between lipid and nonlipid factors and lipoprotein subfractions in infants at birth and follow-up (FU) and in their parents. METHODS: Prospective study in a community-based hospital of 103 families ascertained through a pregnant mother at 36 weeks gestation or older. Of 103 infants studied at birth, 85 were sampled at FU at 2-3 months of age, along with 76 fathers. Lipids, lipoproteins, and their subclasses were determined by nuclear magnetic resonance spectroscopy. Correlations of lipid-related parameters were calculated using Spearman rank correlations. RESULTS: Female gender in infants and use of formula only were the only nonlipid variables associated with lipoprotein subfractions. LDL parameters were significantly correlated between infants at birth and FU. The largest high-density lipoprotein subfraction, H5C, was the only lipid variable significantly associated between mothers and infants at birth. Paternal low-density lipoprotein size was significantly correlated with that of infants at FU but not at birth. In each of the four groups, markedly inverse interrelationships were found between H5C and small LDL particles. At birth and at FU, apoC-I was strongly related with H5C but not TG. Conversely, apoC-I in the parents was strongly related with TG but not H5C. CONCLUSION: Significant relationships were found between lipoprotein subfractions within infants at birth and FU and their parents. ApoC-I and H5C levels very early in life may affect the development of dyslipidemia and obesity in childhood.

A large high-density lipoprotein enriched in apolipoprotein C-I: a novel biochemical marker in infants of lower birth weight and younger gestational age.

CONTEXT: Low birth weight is associated with increased cardiovascular disease in adulthood, and differences in the molecular weight, composition, and quantity of lipoprotein subclasses are associated with coronary artery disease. OBJECTIVE: To determine if there are novel patterns of lipoprotein heterogeneity in low-birth-weight infants. DESIGN, SETTING, AND PARTICIPANTS: Prospective study at a US medical center of a representative sample of infants (n = 163; 70 white and 93 black) born at 28 or more weeks of gestational age between January 3, 2000, and September 27, 2000. This sample constituted 20% of all infants born during the study period at this site. MAIN OUTCOME MEASURES: Plasma levels and particle sizes of lipoprotein subclasses and plasma concentrations of lipids, lipoproteins (high-density lipoprotein [HDL] and low-density lipoprotein [LDL]), and apolipoproteins. RESULTS: An elevated lipoprotein peak of a particle with density between 1.062 and 1.072 g/mL was identified using physical-chemical methods. This subclass of large HDL was enriched in apolipoprotein C-I (apo C-I). Based on the amount of the apo C-I-enriched HDL peak, 156 infants were assigned to 1 of 4 groups: 0 (none detected), 17%; 1 (possibly present), 41%; 2 (probably present), 22%; 3 (elevated), 19%. Infants in group 3, compared with those in the other 3 groups, had significantly (P<.001) lower mean birth weight (2683.7 vs 3307.1 g) and younger mean gestational age (36.2 vs 39.3 wk). After correction for age, infants in group 3 had significantly higher levels of total and large HDL cholesterol and of total and large LDL cholesterol and LDL particle number. However, infants in group 3 had lower levels of small HDL, very low-density lipoproteins, and triglycerides than infants in the other 3 groups. This lipoprotein profile differed from that in infants born small for gestational age, who had significantly higher triglyceride (P<.001) and apo B (P = .04) levels, but lower levels of total and large HDL cholesterol (P<.001) and apo A-I (P<.001). CONCLUSIONS: Because apo C-I-enriched HDL, and purified apo C-I alone, promotes apoptosis in vitro, increased amounts of this particle may have physiological significance and identify a novel group of low-birth-weight infants apparently distinct from traditionally classified small-for-gestational-age infants.

Lipoprotein heterogeneity at birth: influence of gestational age and race on lipoprotein subclasses and Lp (a) lipoprotein.

OBJECTIVE: To determine the influence of gestational age, gender, and race, on lipoprotein heterogeneity at birth. DESIGN: Prospective study of representative sample of infants. SETTING: The Johns Hopkins Hospital. PARTICIPANTS: 163 infants (70 White and 93 Black) >28 weeks gestational age. INTERVENTION: None. MAIN OUTCOME MEASURES: Lipids, lipoprotein subclasses, apolipoproteins, Lp (a) lipoprotein. RESULTS: The number of low-density lipoprotein (LDL) particles, large LDL subclass, and LDL cholesterol level, were all significantly higher in the younger infants. The large high-density lipoprotein (HDL) subclass was significantly higher, while the small HDL subclass was significantly lower in the younger infants. Female infants had a greater HDL size than did males (P=.03). There were no differences between the age groups for HDL cholesterol, very low-density lipoprotein subclasses, or levels of triglycerides, or apolipoproteins B and A-I. White infants had a notably higher mean (SD) level (nmol/L) of total LDL particles (476 [251]), compared to the Black infants (372 [177]) (P=.009). The Black infants had a significantly (P=.02) higher mean (SD) Lp (a) lipoprotein level (mg/dL), compared to the White infants, 2.8 (3.2) vs 1.7 (2.4). Black small-for-gestational age infants had significantly higher levels of very low and intermediate density lipoproteins and apolipoprotein B, compared to appropriate-for-gestational age infants. CONCLUSIONS: Gestational age has a significant effect on both LDL and HDL subclasses. Differences in LDL particle number and Lp (a) between White and Black infants mirror those seen later in life.

Apolipoprotein C-I induces apoptosis in human aortic smooth muscle cells via recruiting neutral sphingomyelinase.

OBJECTIVE: Apolipoprotein C-I (apoC-I) influences lipoprotein metabolism, but little is known about its cellular effects in aortic smooth muscle cells (ASMC). METHODS AND RESULTS: In cultured human ASMC, apoC-I and immunoaffinity purified apoC-I-enriched high-density lipoproteins (HDL) markedly induced apoptosis (5- to 25-fold), compared with control cells, apoC-I-poor HDL, and apolipoprotein C-III (apoC-III) as determined by 4', 6-diamidino-2-phenylindole dihydrochloride staining and DNA ladder assay. Preincubation of cells with GW4869, an inhibitor of neutral sphingomyelinase (N-SMase), blocked apoC-I-induced apoptosis, an effect that was bypassed by C-2 ceramide. The activity of N-SMase was increased 2- to 3-fold in ASMC by apoC-I, apoC-I-enriched HDL, and tumor necrosis factor alpha (TNF-alpha) (positive control) after 10 minutes and then decreased over 60 minutes, which is a kinetic pattern not seen with controls, apoC-III, and apoC-I-poor HDL. ApoC-I and apoC-I-enriched HDL stimulated the generation of ceramide, the release of cytochrome c from mitochondria, and activation of caspase-3 greater than that found in controls, apoC-III, and apoC-I-poor HDL. GW4869 inhibited apoC-I-induced production of ceramide and cytochrome c release. CONCLUSIONS: ApoC-I and apoC-I-enriched HDL activate the N-SMase-ceramide signaling pathway, leading to apoptosis in human ASMC, which is an effect that may promote plaque rupture in vivo.

Response of obligate heterozygotes for phytosterolemia to a low-fat diet and to a plant sterol ester dietary challenge.

Twelve obligate heterozygotes from two kindreds were ascertained through phytosterolemic probands homozygous for molecular defects in the ATP binding cassette (ABC) half transporter, ABCG8. The response of these heterozygotes to a Step 1 diet low in fat, saturated fat, and cholesterol, and to 2.2 g daily of plant sterols (as esters) was determined in Protocol I (16 weeks) and Protocol II (28 weeks) during three consecutive feeding periods: Step 1/placebo spread; Step 1/plant sterol spread; and Step 1/placebo spread (washout). At baseline, half the heterozygotes had moderate dyslipidemia and one-third had mildly elevated campesterol and sitosterol levels. On the Step 1/placebo spread, mean LDL cholesterol decreased significantly, 11.2% in Protocol I (n = 12), and 16.0% in Protocol II (n = 7). Substitution with plant sterol spread produced a significant treatment effect on LDL levels in Protocols I and II. Conversely, the mean levels of campesterol and sitosterol increased 119% and 54%, respectively, during the use of plant sterol spread for 6 weeks in Protocol I, an effect mirrored for 12 weeks in Protocol II. During the placebo spread washouts, LDL levels increased, while those of plant sterols decreased to baseline levels in both protocols. In conclusion, phytosterolemic heterozygotes respond well to a Step 1 diet, and their response to a plant sterol ester challenge appears similar to that observed in normals.