Different Effects of Subclasses of HDL Containing ApoA-I but Not ApoA-II (LpA-I) on Cholesterol Esterification in Plasma and Net Cholesterol Efflux From Foam Cells

Ohta, Takao; Saku, Keijiro; Takata, Kazuhide; Nakamura, Rie; Ikeda, Yukie; Matsuda, Ichiro

doi:10.1161/01.atv.15.7.956

Cited by 37 publications

(29 citation statements)

References 43 publications

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“…Alternatively, HDL from the SLOS fetus was smaller than the other sources of HDL, even the fetal control HDL. It has been suggested previously that smaller HDL particles may be more efficient cholesterol acceptors than larger particles, which is consistent with our results [55,56]. The observed differences in cholesterol efflux were probably not due to differences in the apolipoprotein content of the SLOS HDL particles since there were no gross differences in the SDS gel protein profiles for the different samples.…”

Section: Discussionsupporting

confidence: 92%

Enhanced placental cholesterol efflux by fetal HDL in Smith–Lemli–Opitz syndrome

Jenkins

Merkens

Tubb

et al. 2008

Molecular Genetics and Metabolism

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Previous studies from this laboratory have shown that maternal-derived cholesterol can be effluxed from trophoblasts to fetal HDL and plasma. We had the opportunity to study for the first time the ability of HDL and plasma from a fetus with the Smith-Lemli-Opitz syndrome (SLOS) to efflux cholesterol from trophoblasts. It was unclear whether cholesterol could be effluxed to fetuses with SLOS since lipoprotein levels are often very low. To answer this question, cord blood was collected from the placentas of an SLOS fetus and unaffected fetuses just after delivery. Plasma cholesterol concentrations were very low in the affected fetus; cholesterol, 7-dehydrocholesterol, and 8-dehydocholesterol concentrations were 14.1, 4.5, and 5.2 mg/dl, respectively. The HDL from the fetal SLOS effluxed ≈50% more cholesterol from a trophoblast cell line, were smaller in size, and had a lower cholesterol to phospholipid ratio as compared to HDL from unaffected fetuses or adults. Plasma from the SLOS fetus effluxed cholesterol to a similar percentage as unaffected fetal plasma or adult plasma, possibly due to fewer HDL particles as demonstrated in previous SLOS patients. These novel data demonstrate that the cholesteroldeficient SLOS fetus is able to obtain cholesterol from trophoblasts at a time when cholesterol is playing a critical role in development, and has implications for design of treatments for cholesterol deficiency syndromes as well as understanding of prenatal cholesterol transport in humans. KeywordsFetus; Trophoblast; BeWo cells; Pregnancy; Cholesterol transport Smith-Lemli-Opitz syndrome (SLOS) is a metabolic disorder that presents with a spectrum of congenital abnormalities. Individuals with a severe phenotype have many congenital abnormalities and mental retardation whereas those with a mild phenotype may have only subtle learning disorders and minor dysmorphic features [1][2][3]. The biochemical cause of this syndrome is a reduction in the activity of the enzyme 7-dehydrocholesterol-Δ7- [4,5], which converts 7-dehydrocholesterol (7-DHC) to cholesterol, due to mutations in DHCR7 [6][7][8]. As might be expected, SLOS is characterized by a reduction in cholesterol and an increase in cholesterol precursors, including 7-and 8-DHC. Recent studies demonstrate that the incidence of this syndrome may be much greater than previously believed at a predicted incidence of 1:1590-1:13,500 [9,10], though observed incidence is lower (perhaps 1 in 20,000 births). The discrepancy in observed versus predicted incidence is likely due in part to pregnancy loss as well as undiagnosed mild cases. Nevertheless, SLOS is probably the second most prevalent, potentially lethal, recessive genetic condition behind cystic fibrosis with an incidence of 1:2500 [11]. The congenital malformations associated with this disease can begin to appear as early as 3 weeks postconception when Sonic Hedgehog (SHH) is needed for patterning of the forebrain [12,13], since sterols activate SHH [14][15][16] and sterol deficiency is thought to play a rol...

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Section: Discussionsupporting

confidence: 92%

Enhanced placental cholesterol efflux by fetal HDL in Smith–Lemli–Opitz syndrome

Jenkins

Merkens

Tubb

et al. 2008

Molecular Genetics and Metabolism

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“…ApoAI is distributed approximately equally between LpAI and LpAI/AII, whereas virtually all apoAII is to be found in LpAI/A-II. The HDL2 particle is more abundant in apoAI than in apoAII, whereas apoAI and apoAII are equally distributed in the HDL3 particle [4,31]. Thus, we know that LpAI is more strongly associated with HDL2-apoAI than with HDL3-apoAI.…”

Section: Discussionmentioning

confidence: 97%

“…Thus, we know that LpAI is more strongly associated with HDL2-apoAI than with HDL3-apoAI. Most clinical and clinical studies have agreed that the levels of LpAI are inversely associated with the risk of CHD [31,32]. As such, we know that HDL2-apoAI is probably superior to total apoAI or HDL3-apoAI as a negative risk marker for CHD events.…”

Section: Discussionmentioning

confidence: 99%

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High-density lipoprotein subspecies between patients with type 1 diabetes and type 2 diabetes without / with intensive insulin therapy

Fukui

Hirano

2012

Endocr J

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“…10 Small, dense, lipid-poor HDL3 display higher capacity to accept cholesterol, 11 to inhibit expression of adhesion molecules on endothelial cells in vitro, 12 and to protect LDL from oxidative stress [13][14][15] as compared with large, light, lipid-rich HDL2. The intravascular metabolism and particle heterogeneity of HDL are altered in HALP.…”

mentioning

confidence: 99%

Antioxidative Activity of HDL Particle Subspecies Is Impaired in Hyperalphalipoproteinemia: Relevance of Enzymatic and Physicochemical Properties

Kontush

Faria

Chantepie

et al. 2004

ATVB

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Objective-Hyperalphalipoproteinemia (HALP) is characterized by elevated plasma levels of high-density lipoprotein (HDL) particles with altered composition, metabolism, and function. The impact of such modification on antioxidative activities of HDL subfractions is indeterminate. Methods and Results-Gradient fractionation revealed that buoyant HDL2b and 2a and small dense HDL3b and 3c levels were elevated up to 2.0-fold in HALP subjects (nϭ9; mean plasma HDL cholesterol, 79 mg/dL) with low hepatic lipase activity. HDL2a, 3a, 3b, and 3c displayed lower specific antioxidative activity (sAA) during low-density lipoprotein (LDL) oxidation (Ϫ15% to Ϫ86%, on a unit particle mass basis) than their normolipidemic counterparts (nϭ13). LDL oxidation was delayed by control HDL3a, 3b, and 3c (up to Ϫ79%) but specifically by HDL3c (Ϫ54%) in HALP. Paraoxonase activity was deficient in all HALP HDL subfractions. Paraoxonase, PAF-AH, and LCAT activities together accounted for Ϸ50% of variation in sAA. Abnormal chemical composition of HDL3b and 3c (cholesterol-deficient, triglyceride-enriched) in HALP was associated with impaired sAA. Systemic oxidative stress (as plasma 8-isoprostanes) tended to be elevated (1.5-fold) in HALP and negatively correlated with sAA (as TBARS). Conclusions-Intrinsic

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Different Effects of Subclasses of HDL Containing ApoA-I but Not ApoA-II (LpA-I) on Cholesterol Esterification in Plasma and Net Cholesterol Efflux From Foam Cells

Cited by 37 publications

References 43 publications

Enhanced placental cholesterol efflux by fetal HDL in Smith–Lemli–Opitz syndrome

Enhanced placental cholesterol efflux by fetal HDL in Smith–Lemli–Opitz syndrome

High-density lipoprotein subspecies between patients with type 1 diabetes and type 2 diabetes without / with intensive insulin therapy

Antioxidative Activity of HDL Particle Subspecies Is Impaired in Hyperalphalipoproteinemia: Relevance of Enzymatic and Physicochemical Properties

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